Author: "Gonneke Willemsen" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Gonneke Willemsen"' showing total 538 results

Start Over Author "Gonneke Willemsen"

538 results on '"Gonneke Willemsen"'

51. The molecular genetic architecture of self-employment.

Author: Matthijs J H M van der Loos, Cornelius A Rietveld, Niina Eklund, Philipp D Koellinger, Fernando Rivadeneira, Gonçalo R Abecasis, Georgina A Ankra-Badu, Sebastian E Baumeister, Daniel J Benjamin, Reiner Biffar, Stefan Blankenberg, Dorret I Boomsma, David Cesarini, Francesco Cucca, Eco J C de Geus, George Dedoussis, Panos Deloukas, Maria Dimitriou, Guðny Eiriksdottir, Johan Eriksson, Christian Gieger, Vilmundur Gudnason, Birgit Höhne, Rolf Holle, Jouke-Jan Hottenga, Aaron Isaacs, Marjo-Riitta Järvelin, Magnus Johannesson, Marika Kaakinen, Mika Kähönen, Stavroula Kanoni, Maarit A Laaksonen, Jari Lahti, Lenore J Launer, Terho Lehtimäki, Marisa Loitfelder, Patrik K E Magnusson, Silvia Naitza, Ben A Oostra, Markus Perola, Katja Petrovic, Lydia Quaye, Olli Raitakari, Samuli Ripatti, Paul Scheet, David Schlessinger, Carsten O Schmidt, Helena Schmidt, Reinhold Schmidt, Andrea Senft, Albert V Smith, Timothy D Spector, Ida Surakka, Rauli Svento, Antonio Terracciano, Emmi Tikkanen, Cornelia M van Duijn, Jorma Viikari, Henry Völzke, H-Erich Wichmann, Philipp S Wild, Sara M Willems, Gonneke Willemsen, Frank J A van Rooij, Patrick J F Groenen, André G Uitterlinden, Albert Hofman, and A Roy Thurik
Subjects: Medicine, Science
Abstract: Economic variables such as income, education, and occupation are known to affect mortality and morbidity, such as cardiovascular disease, and have also been shown to be partly heritable. However, very little is known about which genes influence economic variables, although these genes may have both a direct and an indirect effect on health. We report results from the first large-scale collaboration that studies the molecular genetic architecture of an economic variable-entrepreneurship-that was operationalized using self-employment, a widely-available proxy. Our results suggest that common SNPs when considered jointly explain about half of the narrow-sense heritability of self-employment estimated in twin data (σ(g)(2)/σ(P)(2) = 25%, h(2) = 55%). However, a meta-analysis of genome-wide association studies across sixteen studies comprising 50,627 participants did not identify genome-wide significant SNPs. 58 SNPs with p
Published: 2013
Full Text: View/download PDF

52. The role of adiposity in cardiometabolic traits: a Mendelian randomization analysis.

Author: Tove Fall, Sara Hägg, Reedik Mägi, Alexander Ploner, Krista Fischer, Momoko Horikoshi, Antti-Pekka Sarin, Gudmar Thorleifsson, Claes Ladenvall, Mart Kals, Maris Kuningas, Harmen H M Draisma, Janina S Ried, Natalie R van Zuydam, Ville Huikari, Massimo Mangino, Emily Sonestedt, Beben Benyamin, Christopher P Nelson, Natalia V Rivera, Kati Kristiansson, Huei-Yi Shen, Aki S Havulinna, Abbas Dehghan, Louise A Donnelly, Marika Kaakinen, Marja-Liisa Nuotio, Neil Robertson, Renée F A G de Bruijn, M Arfan Ikram, Najaf Amin, Anthony J Balmforth, Peter S Braund, Alexander S F Doney, Angela Döring, Paul Elliott, Tõnu Esko, Oscar H Franco, Solveig Gretarsdottir, Anna-Liisa Hartikainen, Kauko Heikkilä, Karl-Heinz Herzig, Hilma Holm, Jouke Jan Hottenga, Elina Hyppönen, Thomas Illig, Aaron Isaacs, Bo Isomaa, Lennart C Karssen, Johannes Kettunen, Wolfgang Koenig, Kari Kuulasmaa, Tiina Laatikainen, Jaana Laitinen, Cecilia Lindgren, Valeriya Lyssenko, Esa Läärä, Nigel W Rayner, Satu Männistö, Anneli Pouta, Wolfgang Rathmann, Fernando Rivadeneira, Aimo Ruokonen, Markku J Savolainen, Eric J G Sijbrands, Kerrin S Small, Jan H Smit, Valgerdur Steinthorsdottir, Ann-Christine Syvänen, Anja Taanila, Martin D Tobin, Andre G Uitterlinden, Sara M Willems, Gonneke Willemsen, Jacqueline Witteman, Markus Perola, Alun Evans, Jean Ferrières, Jarmo Virtamo, Frank Kee, David-Alexandre Tregouet, Dominique Arveiler, Philippe Amouyel, Marco M Ferrario, Paolo Brambilla, Alistair S Hall, Andrew C Heath, Pamela A F Madden, Nicholas G Martin, Grant W Montgomery, John B Whitfield, Antti Jula, Paul Knekt, Ben Oostra, Cornelia M van Duijn, Brenda W J H Penninx, George Davey Smith, Jaakko Kaprio, Nilesh J Samani, Christian Gieger, Annette Peters, H Erich Wichmann, Dorret I Boomsma, Eco J C de Geus, TiinaMaija Tuomi, Chris Power, Christopher J Hammond, Tim D Spector, Lars Lind, Marju Orho-Melander, Colin Neil Alexander Palmer, Andrew D Morris, Leif Groop, Marjo-Riitta Järvelin, Veikko Salomaa, Erkki Vartiainen, Albert Hofman, Samuli Ripatti, Andres Metspalu, Unnur Thorsteinsdottir, Kari Stefansson, Nancy L Pedersen, Mark I McCarthy, Erik Ingelsson, Inga Prokopenko, and European Network for Genetic and Genomic Epidemiology (ENGAGE) consortium
Subjects: Medicine
Abstract: BackgroundThe association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach.Methods and findingsWe used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age- and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p < 0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p < 0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (p = 0.001).ConclusionsWe provide novel evidence for a causal relationship between adiposity and heart failure as well as between adiposity and increased liver enzymes.
Published: 2013
Full Text: View/download PDF

53. Sex differences in genetic architecture of complex phenotypes?

Author: Jacqueline M Vink, Meike Bartels, Toos C E M van Beijsterveldt, Jenny van Dongen, Jenny H D A van Beek, Marijn A Distel, Marleen H M de Moor, Dirk J A Smit, Camelia C Minica, Lannie Ligthart, Lot M Geels, Abdel Abdellaoui, Christel M Middeldorp, Jouke Jan Hottenga, Gonneke Willemsen, Eco J C de Geus, and Dorret I Boomsma
Subjects: Medicine, Science
Abstract: We examined sex differences in familial resemblance for a broad range of behavioral, psychiatric and health related phenotypes (122 complex traits) in children and adults. There is a renewed interest in the importance of genotype by sex interaction in, for example, genome-wide association (GWA) studies of complex phenotypes. If different genes play a role across sex, GWA studies should consider the effect of genetic variants separately in men and women, which affects statistical power. Twin and family studies offer an opportunity to compare resemblance between opposite-sex family members to the resemblance between same-sex relatives, thereby presenting a test of quantitative and qualitative sex differences in the genetic architecture of complex traits. We analyzed data on lifestyle, personality, psychiatric disorder, health, growth, development and metabolic traits in dizygotic (DZ) same-sex and opposite-sex twins, as these siblings are perfectly matched for age and prenatal exposures. Sample size varied from slightly over 300 subjects for measures of brain function such as EEG power to over 30,000 subjects for childhood psychopathology and birth weight. For most phenotypes, sample sizes were large, with an average sample size of 9027 individuals. By testing whether the resemblance in DZ opposite-sex pairs is the same as in DZ same-sex pairs, we obtain evidence for genetic qualitative sex-differences in the genetic architecture of complex traits for 4% of phenotypes. We conclude that for most traits that were examined, the current evidence is that same the genes are operating in men and women.
Published: 2012
Full Text: View/download PDF

54. Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Author: Zari Dastani, Marie-France Hivert, Nicholas Timpson, John R B Perry, Xin Yuan, Robert A Scott, Peter Henneman, Iris M Heid, Jorge R Kizer, Leo-Pekka Lyytikäinen, Christian Fuchsberger, Toshiko Tanaka, Andrew P Morris, Kerrin Small, Aaron Isaacs, Marian Beekman, Stefan Coassin, Kurt Lohman, Lu Qi, Stavroula Kanoni, James S Pankow, Hae-Won Uh, Ying Wu, Aurelian Bidulescu, Laura J Rasmussen-Torvik, Celia M T Greenwood, Martin Ladouceur, Jonna Grimsby, Alisa K Manning, Ching-Ti Liu, Jaspal Kooner, Vincent E Mooser, Peter Vollenweider, Karen A Kapur, John Chambers, Nicholas J Wareham, Claudia Langenberg, Rune Frants, Ko Willems-Vandijk, Ben A Oostra, Sara M Willems, Claudia Lamina, Thomas W Winkler, Bruce M Psaty, Russell P Tracy, Jennifer Brody, Ida Chen, Jorma Viikari, Mika Kähönen, Peter P Pramstaller, David M Evans, Beate St Pourcain, Naveed Sattar, Andrew R Wood, Stefania Bandinelli, Olga D Carlson, Josephine M Egan, Stefan Böhringer, Diana van Heemst, Lyudmyla Kedenko, Kati Kristiansson, Marja-Liisa Nuotio, Britt-Marie Loo, Tamara Harris, Melissa Garcia, Alka Kanaya, Margot Haun, Norman Klopp, H-Erich Wichmann, Panos Deloukas, Efi Katsareli, David J Couper, Bruce B Duncan, Margreet Kloppenburg, Linda S Adair, Judith B Borja, DIAGRAM+ Consortium, MAGIC Consortium, GLGC Investigators, MuTHER Consortium, James G Wilson, Solomon Musani, Xiuqing Guo, Toby Johnson, Robert Semple, Tanya M Teslovich, Matthew A Allison, Susan Redline, Sarah G Buxbaum, Karen L Mohlke, Ingrid Meulenbelt, Christie M Ballantyne, George V Dedoussis, Frank B Hu, Yongmei Liu, Bernhard Paulweber, Timothy D Spector, P Eline Slagboom, Luigi Ferrucci, Antti Jula, Markus Perola, Olli Raitakari, Jose C Florez, Veikko Salomaa, Johan G Eriksson, Timothy M Frayling, Andrew A Hicks, Terho Lehtimäki, George Davey Smith, David S Siscovick, Florian Kronenberg, Cornelia van Duijn, Ruth J F Loos, Dawn M Waterworth, James B Meigs, Josee Dupuis, J Brent Richards, Benjamin F Voight, Laura J Scott, Valgerdur Steinthorsdottir, Christian Dina, Ryan P Welch, Eleftheria Zeggini, Cornelia Huth, Yurii S Aulchenko, Gudmar Thorleifsson, Laura J McCulloch, Teresa Ferreira, Harald Grallert, Najaf Amin, Guanming Wu, Cristen J Willer, Soumya Raychaudhuri, Steve A McCarroll, Oliver M Hofmann, Ayellet V Segrè, Mandy van Hoek, Pau Navarro, Kristin Ardlie, Beverley Balkau, Rafn Benediktsson, Amanda J Bennett, Roza Blagieva, Eric Boerwinkle, Lori L Bonnycastle, Kristina Bengtsson Boström, Bert Bravenboer, Suzannah Bumpstead, Noël P Burtt, Guillaume Charpentier, Peter S Chines, Marilyn Cornelis, Gabe Crawford, Alex S F Doney, Katherine S Elliott, Amanda L Elliott, Michael R Erdos, Caroline S Fox, Christopher S Franklin, Martha Ganser, Christian Gieger, Niels Grarup, Todd Green, Simon Griffin, Christopher J Groves, Candace Guiducci, Samy Hadjadj, Neelam Hassanali, Christian Herder, Bo Isomaa, Anne U Jackson, Paul R V Johnson, Torben Jørgensen, Wen H L Kao, Augustine Kong, Peter Kraft, Johanna Kuusisto, Torsten Lauritzen, Man Li, Aloysius Lieverse, Cecilia M Lindgren, Valeriya Lyssenko, Michel Marre, Thomas Meitinger, Kristian Midthjell, Mario A Morken, Narisu Narisu, Peter Nilsson, Katharine R Owen, Felicity Payne, Ann-Kristin Petersen, Carl Platou, Christine Proença, Inga Prokopenko, Wolfgang Rathmann, N William Rayner, Neil R Robertson, Ghislain Rocheleau, Michael Roden, Michael J Sampson, Richa Saxena, Beverley M Shields, Peter Shrader, Gunnar Sigurdsson, Thomas Sparsø, Klaus Strassburger, Heather M Stringham, Qi Sun, Amy J Swift, Barbara Thorand, Jean Tichet, Tiinamaija Tuomi, Rob M van Dam, Timon W van Haeften, Thijs van Herpt, Jana V van Vliet-Ostaptchouk, G Bragi Walters, Michael N Weedon, Cisca Wijmenga, Jacqueline Witteman, Richard N Bergman, Stephane Cauchi, Francis S Collins, Anna L Gloyn, Ulf Gyllensten, Torben Hansen, Winston A Hide, Graham A Hitman, Albert Hofman, David J Hunter, Kristian Hveem, Markku Laakso, Andrew D Morris, Colin N A Palmer, Igor Rudan, Eric Sijbrands, Lincoln D Stein, Jaakko Tuomilehto, Andre Uitterlinden, Mark Walker, Richard M Watanabe, Goncalo R Abecasis, Bernhard O Boehm, Harry Campbell, Mark J Daly, Andrew T Hattersley, Oluf Pedersen, Inês Barroso, Leif Groop, Rob Sladek, Unnur Thorsteinsdottir, James F Wilson, Thomas Illig, Philippe Froguel, Cornelia M van Duijn, Kari Stefansson, David Altshuler, Michael Boehnke, Mark I McCarthy, Nicole Soranzo, Eleanor Wheeler, Nicole L Glazer, Nabila Bouatia-Naji, Reedik Mägi, Joshua Randall, Paul Elliott, Denis Rybin, Abbas Dehghan, Jouke Jan Hottenga, Kijoung Song, Anuj Goel, Taina Lajunen, Alex Doney, Christine Cavalcanti-Proença, Meena Kumari, Nicholas J Timpson, Carina Zabena, Erik Ingelsson, Ping An, Jeffrey O'Connell, Jian'an Luan, Amanda Elliott, Steven A McCarroll, Rosa Maria Roccasecca, François Pattou, Praveen Sethupathy, Yavuz Ariyurek, Philip Barter, John P Beilby, Yoav Ben-Shlomo, Sven Bergmann, Murielle Bochud, Amélie Bonnefond, Knut Borch-Johnsen, Yvonne Böttcher, Eric Brunner, Suzannah J Bumpstead, Yii-Der Ida Chen, Peter Chines, Robert Clarke, Lachlan J M Coin, Matthew N Cooper, Laura Crisponi, Ian N M Day, Eco J C de Geus, Jerome Delplanque, Annette C Fedson, Antje Fischer-Rosinsky, Nita G Forouhi, Maria Grazia Franzosi, Pilar Galan, Mark O Goodarzi, Jürgen Graessler, Scott Grundy, Rhian Gwilliam, Göran Hallmans, Naomi Hammond, Xijing Han, Anna-Liisa Hartikainen, Caroline Hayward, Simon C Heath, Serge Hercberg, David R Hillman, Aroon D Hingorani, Jennie Hui, Joe Hung, Marika Kaakinen, Jaakko Kaprio, Y Antero Kesaniemi, Mika Kivimaki, Beatrice Knight, Seppo Koskinen, Peter Kovacs, Kirsten Ohm Kyvik, G Mark Lathrop, Debbie A Lawlor, Olivier Le Bacquer, Cécile Lecoeur, Yun Li, Robert Mahley, Massimo Mangino, María Teresa Martínez-Larrad, Jarred B McAteer, Ruth McPherson, Christa Meisinger, David Melzer, David Meyre, Braxton D Mitchell, Sutapa Mukherjee, Silvia Naitza, Matthew J Neville, Marco Orrù, Ruth Pakyz, Giuseppe Paolisso, Cristian Pattaro, Daniel Pearson, John F Peden, Nancy L Pedersen, Andreas F H Pfeiffer, Irene Pichler, Ozren Polasek, Danielle Posthuma, Simon C Potter, Anneli Pouta, Michael A Province, Nigel W Rayner, Kenneth Rice, Samuli Ripatti, Fernando Rivadeneira, Olov Rolandsson, Annelli Sandbaek, Manjinder Sandhu, Serena Sanna, Avan Aihie Sayer, Paul Scheet, Udo Seedorf, Stephen J Sharp, Beverley Shields, Gunnar Sigurðsson, Eric J G Sijbrands, Angela Silveira, Laila Simpson, Andrew Singleton, Nicholas L Smith, Ulla Sovio, Amy Swift, Holly Syddall, Ann-Christine Syvänen, Anke Tönjes, André G Uitterlinden, Ko Willems van Dijk, Dhiraj Varma, Sophie Visvikis-Siest, Veronique Vitart, Nicole Vogelzangs, Gérard Waeber, Peter J Wagner, Andrew Walley, Kim L Ward, Hugh Watkins, Sarah H Wild, Gonneke Willemsen, Jaqueline C M Witteman, John W G Yarnell, Diana Zelenika, Björn Zethelius, Guangju Zhai, Jing Hua Zhao, M Carola Zillikens, DIAGRAM Consortium, GIANT Consortium, Global B Pgen Consortium, Ingrid B Borecki, Pierre Meneton, Patrik K E Magnusson, David M Nathan, Gordon H Williams, Kaisa Silander, Stefan R Bornstein, Peter Schwarz, Joachim Spranger, Fredrik Karpe, Alan R Shuldiner, Cyrus Cooper, Manuel Serrano-Ríos, Lars Lind, Lyle J Palmer, Paul W Franks, Shah Ebrahim, Michael Marmot, W H Linda Kao, Peter Paul Pramstaller, Alan F Wright, Michael Stumvoll, Anders Hamsten, Procardis Consortium, Thomas A Buchanan, Timo T Valle, Jerome I Rotter, Brenda W J H Penninx, Dorret I Boomsma, Antonio Cao, Angelo Scuteri, David Schlessinger, Manuela Uda, Aimo Ruokonen, Marjo-Riitta Jarvelin, Leena Peltonen, Vincent Mooser, Robert Sladek, MAGIC investigators, GLGC Consortium, Kiran Musunuru, Albert V Smith, Andrew C Edmondson, Ioannis M Stylianou, Masahiro Koseki, James P Pirruccello, Daniel I Chasman, Christopher T Johansen, Sigrid W Fouchier, Gina M Peloso, Maja Barbalic, Sally L Ricketts, Joshua C Bis, Mary F Feitosa, Marju Orho-Melander, Olle Melander, Xiaohui Li, Mingyao Li, Yoon Shin Cho, Min Jin Go, Young Jin Kim, Jong-Young Lee, Taesung Park, Kyunga Kim, Xueling Sim, Rick Twee-Hee Ong, Damien C Croteau-Chonka, Leslie A Lange, Joshua D Smith, Andreas Ziegler, Weihua Zhang, Robert Y L Zee, John B Whitfield, John R Thompson, Ida Surakka, Tim D Spector, Johannes H Smit, Juha Sinisalo, James Scott, Juha Saharinen, Chiara Sabatti, Lynda M Rose, Robert Roberts, Mark Rieder, Alex N Parker, Guillaume Pare, Christopher J O'Donnell, Markku S Nieminen, Deborah A Nickerson, Grant W Montgomery, Wendy McArdle, David Masson, Nicholas G Martin, Fabio Marroni, Gavin Lucas, Robert Luben, Marja-Liisa Lokki, Guillaume Lettre, Lenore J Launer, Edward G Lakatta, Reijo Laaksonen, Kirsten O Kyvik, Inke R König, Kay-Tee Khaw, Lee M Kaplan, Åsa Johansson, A Cecile J W Janssens, Wilmar Igl, G Kees Hovingh, Christian Hengstenberg, Aki S Havulinna, Nicholas D Hastie, Tamara B Harris, Talin Haritunians, Alistair S Hall, Leif C Groop, Elena Gonzalez, Nelson B Freimer, Jeanette Erdmann, Kenechi G Ejebe, Angela Döring, Anna F Dominiczak, Serkalem Demissie, Panagiotis Deloukas, Ulf de Faire, Gabriel Crawford, Yii-der I Chen, Mark J Caulfield, S Matthijs Boekholdt, Themistocles L Assimes, Thomas Quertermous, Mark Seielstad, Tien Y Wong, E-Shyong Tai, Alan B Feranil, Christopher W Kuzawa, Herman A Taylor, Stacey B Gabriel, Hilma Holm, Vilmundur Gudnason, Ronald M Krauss, Jose M Ordovas, Patricia B Munroe, Jaspal S Kooner, Alan R Tall, Robert A Hegele, John J P Kastelein, Eric E Schadt, David P Strachan, Muredach P Reilly, Nilesh J Samani, Heribert Schunkert, L Adrienne Cupples, Manjinder S Sandhu, Paul M Ridker, Daniel J Rader, and Sekar Kathiresan
Subjects: Genetics, QH426-470
Abstract: Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p
Published: 2012
Full Text: View/download PDF

55. Correction: Common Variants in the Type 2 Diabetes Gene Are Associated with Impairments in Insulin Secretion During Hyperglycaemic Glucose Clamp.

Author: Jana V. van Vliet-Ostaptchouk, Timon W. van Haeften, Gijs W. D. Landman, Erwin Reiling, Nanne Kleefstra, Henk J. G. Bilo, Olaf H. Klungel, Anthonius de Boer, Cleo C. van Diemen, Cisca Wijmenga, H. Marike Boezen, Jacqueline M. Dekker, Esther van 't Riet, Giel Nijpels, Laura M. C. Welschen, Hata Zavrelova, Elinda J. Bruin, Clara C. Elbers, Florianne Bauer, N. Charlotte Onland-Moret, Yvonne T. van der Schouw, Diederick E. Grobbee, Annemieke M. W. Spijkerman, Daphne L. van der A, Annemarie M. Simonis-Bik, Elisabeth M. W. Eekhoff, Michaela Diamant, Mark H. H. Kramer, Dorret I. Boomsma, Eco J. de Geus, Gonneke Willemsen, P. Eline Slagboom, Marten H. Hofker, and Leen M. 't Hart
Subjects: Medicine, Science
Published: 2012
Full Text: View/download PDF

56. A fine-mapping study of 7 top scoring genes from a GWAS for major depressive disorder.

Author: Eva C Verbeek, Ingrid M C Bakker, Marianna R Bevova, Zoltán Bochdanovits, Patrizia Rizzu, David Sondervan, Gonneke Willemsen, Eco J de Geus, Johannes H Smit, Brenda W Penninx, Dorret I Boomsma, Witte J G Hoogendijk, and Peter Heutink
Subjects: Medicine, Science
Abstract: Major depressive disorder (MDD) is a psychiatric disorder that is characterized--amongst others--by persistent depressed mood, loss of interest and pleasure and psychomotor retardation. Environmental circumstances have proven to influence the aetiology of the disease, but MDD also has an estimated 40% heritability, probably with a polygenic background. In 2009, a genome wide association study (GWAS) was performed on the Dutch GAIN-MDD cohort. A non-synonymous coding single nucleotide polymorphism (SNP) rs2522833 in the PCLO gene became only nominally significant after post-hoc analysis with an Australian cohort which used similar ascertainment. The absence of genome-wide significance may be caused by low SNP coverage of genes. To increase SNP coverage to 100% for common variants (m.a.f.>0.1, r(2)>0.8), we selected seven genes from the GAIN-MDD GWAS: PCLO, GZMK, ANPEP, AFAP1L1, ST3GAL6, FGF14 and PTK2B. We genotyped 349 SNPs and obtained the lowest P-value for rs2715147 in PCLO at P = 6.8E-7. We imputed, filling in missing genotypes, after which rs2715147 and rs2715148 showed the lowest P-value at P = 1.2E-6. When we created a haplotype of these SNPs together with the non-synonymous coding SNP rs2522833, the P-value decreased to P = 9.9E-7 but was not genome wide significant. Although our study did not identify a more strongly associated variant, the results for PCLO suggest that the causal variant is in high LD with rs2715147, rs2715148 and rs2522833.
Published: 2012
Full Text: View/download PDF

57. Common variants in the type 2 diabetes KCNQ1 gene are associated with impairments in insulin secretion during hyperglycaemic glucose clamp.

Author: Jana V van Vliet-Ostaptchouk, Timon W van Haeften, Gijs W D Landman, Erwin Reiling, Nanne Kleefstra, Henk J G Bilo, Olaf H Klungel, Anthonius de Boer, Cleo C van Diemen, Cisca Wijmenga, H Marike Boezen, Jacqueline M Dekker, Esther van 't Riet, Giel Nijpels, Laura M C Welschen, Hata Zavrelova, Elinda J Bruin, Clara C Elbers, Florianne Bauer, N Charlotte Onland-Moret, Yvonne T van der Schouw, Diederick E Grobbee, Annemieke M W Spijkerman, Daphne L van der A, Annemarie M Simonis-Bik, Elisabeth M W Eekhoff, Michaela Diamant, Mark H H Kramer, Dorret I Boomsma, Eco J de Geus, Gonneke Willemsen, P Eline Slagboom, Marten H Hofker, and Leen M 't Hart
Subjects: Medicine, Science
Abstract: BACKGROUND:Genome-wide association studies in Japanese populations recently identified common variants in the KCNQ1 gene to be associated with type 2 diabetes. We examined the association of these variants within KCNQ1 with type 2 diabetes in a Dutch population, investigated their effects on insulin secretion and metabolic traits and on the risk of developing complications in type 2 diabetes patients. METHODOLOGY:The KCNQ1 variants rs151290, rs2237892, and rs2237895 were genotyped in a total of 4620 type 2 diabetes patients and 5285 healthy controls from the Netherlands. Data on macrovascular complications, nephropathy and retinopathy were available in a subset of diabetic patients. Association between genotype and insulin secretion/action was assessed in the additional sample of 335 individuals who underwent a hyperglycaemic clamp. PRINCIPAL FINDINGS:We found that all the genotyped KCNQ1 variants were significantly associated with type 2 diabetes in our Dutch population, and the association of rs151290 was the strongest (OR 1.20, 95% CI 1.07-1.35, p = 0.002). The risk C-allele of rs151290 was nominally associated with reduced first-phase glucose-stimulated insulin secretion, while the non-risk T-allele of rs2237892 was significantly correlated with increased second-phase glucose-stimulated insulin secretion (p = 0.025 and 0.0016, respectively). In addition, the risk C-allele of rs2237892 was associated with higher LDL and total cholesterol levels (p = 0.015 and 0.003, respectively). We found no evidence for an association of KCNQ1 with diabetic complications. CONCLUSIONS:Common variants in the KCNQ1 gene are associated with type 2 diabetes in a Dutch population, which can be explained at least in part by an effect on insulin secretion. Furthermore, our data suggest that KCNQ1 is also associated with lipid metabolism.
Published: 2012
Full Text: View/download PDF

58. A genome-wide association search for type 2 diabetes genes in African Americans.

Author: Nicholette D Palmer, Caitrin W McDonough, Pamela J Hicks, Bong H Roh, Maria R Wing, S Sandy An, Jessica M Hester, Jessica N Cooke, Meredith A Bostrom, Megan E Rudock, Matthew E Talbert, Joshua P Lewis, DIAGRAM Consortium, MAGIC Investigators, Assiamira Ferrara, Lingyi Lu, Julie T Ziegler, Michele M Sale, Jasmin Divers, Daniel Shriner, Adebowale Adeyemo, Charles N Rotimi, Maggie C Y Ng, Carl D Langefeld, Barry I Freedman, Donald W Bowden, Benjamin F Voight, Laura J Scott, Valgerdur Steinthorsdottir, Andrew P Morris, Christian Dina, Ryan P Welch, Eleftheria Zeggini, Cornelia Huth, Yurii S Aulchenko, Gudmar Thorleifsson, Laura J McCulloch, Teresa Ferreira, Harald Grallert, Najaf Amin, Guanming Wu, Cristen J Willer, Soumya Raychaudhuri, Steve A McCarroll, Claudia Langenberg, Oliver M Hofmann, Josée Dupuis, Lu Qi, Ayellet V Segrè, Mandy van Hoek, Pau Navarro, Kristin Ardlie, Beverley Balkau, Rafn Benediktsson, Amanda J Bennett, Roza Blagieva, Eric Boerwinkle, Lori L Bonnycastle, Kristina Bengtsson Boström, Bert Bravenboer, Suzannah Bumpstead, Noël P Burtt, Guillaume Charpentier, Peter S Chines, Marilyn Cornelis, David J Couper, Gabe Crawford, Alex S F Doney, Katherine S Elliott, Amanda L Elliott, Michael R Erdos, Caroline S Fox, Christopher S Franklin, Martha Ganser, Christian Gieger, Niels Grarup, Todd Green, Simon Griffin, Christopher J Groves, Candace Guiducci, Samy Hadjadj, Neelam Hassanali, Christian Herder, Bo Isomaa, Anne U Jackson, Paul R V Johnson, Torben Jørgensen, Wen H L Kao, Norman Klopp, Augustine Kong, Peter Kraft, Johanna Kuusisto, Torsten Lauritzen, Man Li, Aloysius Lieverse, Cecilia M Lindgren, Valeriya Lyssenko, Michel Marre, Thomas Meitinger, Kristian Midthjell, Mario A Morken, Narisu Narisu, Peter Nilsson, Katharine R Owen, Felicity Payne, John R B Perry, Ann-Kristin Petersen, Carl Platou, Christine Proença, Inga Prokopenko, Wolfgang Rathmann, N William Rayner, Neil R Robertson, Ghislain Rocheleau, Michael Roden, Michael J Sampson, Richa Saxena, Beverley M Shields, Peter Shrader, Gunnar Sigurdsson, Thomas Sparsø, Klaus Strassburger, Heather M Stringham, Qi Sun, Amy J Swift, Barbara Thorand, Jean Tichet, Tiinamaija Tuomi, Rob M van Dam, Timon W van Haeften, Thijs van Herpt, Jana V van Vliet-Ostaptchouk, G Bragi Walters, Michael N Weedon, Cisca Wijmenga, Jacqueline Witteman, Richard N Bergman, Stephane Cauchi, Francis S Collins, Anna L Gloyn, Ulf Gyllensten, Torben Hansen, Winston A Hide, Graham A Hitman, Albert Hofman, David J Hunter, Kristian Hveem, Markku Laakso, Karen L Mohlke, Andrew D Morris, Colin N A Palmer, Peter P Pramstaller, Igor Rudan, Eric Sijbrands, Lincoln D Stein, Jaakko Tuomilehto, Andre Uitterlinden, Mark Walker, Nicholas J Wareham, Richard M Watanabe, Goncalo R Abecasis, Bernhard O Boehm, Harry Campbell, Mark J Daly, Andrew T Hattersley, Frank B Hu, James B Meigs, James S Pankow, Oluf Pedersen, H-Erich Wichmann, Inês Barroso, Jose C Florez, Timothy M Frayling, Leif Groop, Rob Sladek, Unnur Thorsteinsdottir, James F Wilson, Thomas Illig, Philippe Froguel, Cornelia M van Duijn, Kari Stefansson, David Altshuler, Michael Boehnke, Mark I McCarthy, Nicole Soranzo, Eleanor Wheeler, Nicole L Glazer, Nabila Bouatia-Naji, Reedik Mägi, Joshua Randall, Toby Johnson, Paul Elliott, Denis Rybin, Peter Henneman, Abbas Dehghan, Jouke Jan Hottenga, Kijoung Song, Anuj Goel, Josephine M Egan, Taina Lajunen, Alex Doney, Stavroula Kanoni, Christine Cavalcanti-Proença, Meena Kumari, Nicholas J Timpson, Carina Zabena, Erik Ingelsson, Ping An, Jeffrey O'Connell, Jian'an Luan, Amanda Elliott, Steven A McCarroll, Rosa Maria Roccasecca, François Pattou, Praveen Sethupathy, Yavuz Ariyurek, Philip Barter, John P Beilby, Yoav Ben-Shlomo, Sven Bergmann, Murielle Bochud, Amélie Bonnefond, Knut Borch-Johnsen, Yvonne Böttcher, Eric Brunner, Suzannah J Bumpstead, Yii-Der Ida Chen, Peter Chines, Robert Clarke, Lachlan J M Coin, Matthew N Cooper, Laura Crisponi, Ian N M Day, Eco J C de Geus, Jerome Delplanque, Annette C Fedson, Antje Fischer-Rosinsky, Nita G Forouhi, Rune Frants, Maria Grazia Franzosi, Pilar Galan, Mark O Goodarzi, Jürgen Graessler, Scott Grundy, Rhian Gwilliam, Göran Hallmans, Naomi Hammond, Xijing Han, Anna-Liisa Hartikainen, Caroline Hayward, Simon C Heath, Serge Hercberg, Andrew A Hicks, David R Hillman, Aroon D Hingorani, Jennie Hui, Joe Hung, Antti Jula, Marika Kaakinen, Jaakko Kaprio, Y Antero Kesaniemi, Mika Kivimaki, Beatrice Knight, Seppo Koskinen, Peter Kovacs, Kirsten Ohm Kyvik, G Mark Lathrop, Debbie A Lawlor, Olivier Le Bacquer, Cécile Lecoeur, Yun Li, Robert Mahley, Massimo Mangino, Alisa K Manning, María Teresa Martínez-Larrad, Jarred B McAteer, Ruth McPherson, Christa Meisinger, David Melzer, David Meyre, Braxton D Mitchell, Sutapa Mukherjee, Silvia Naitza, Matthew J Neville, Ben A Oostra, Marco Orrù, Ruth Pakyz, Giuseppe Paolisso, Cristian Pattaro, Daniel Pearson, John F Peden, Nancy L Pedersen, Markus Perola, Andreas F H Pfeiffer, Irene Pichler, Ozren Polasek, Danielle Posthuma, Simon C Potter, Anneli Pouta, Michael A Province, Bruce M Psaty, Nigel W Rayner, Kenneth Rice, Samuli Ripatti, Fernando Rivadeneira, Olov Rolandsson, Annelli Sandbaek, Manjinder Sandhu, Serena Sanna, Avan Aihie Sayer, Paul Scheet, Udo Seedorf, Stephen J Sharp, Beverley Shields, Eric J G Sijbrands, Angela Silveira, Laila Simpson, Andrew Singleton, Nicholas L Smith, Ulla Sovio, Amy Swift, Holly Syddall, Ann-Christine Syvänen, Toshiko Tanaka, Anke Tönjes, André G Uitterlinden, Ko Willems van Dijk, Dhiraj Varma, Sophie Visvikis-Siest, Veronique Vitart, Nicole Vogelzangs, Gérard Waeber, Peter J Wagner, Andrew Walley, Kim L Ward, Hugh Watkins, Sarah H Wild, Gonneke Willemsen, Jaqueline C M Witteman, John W G Yarnell, Diana Zelenika, Björn Zethelius, Guangju Zhai, Jing Hua Zhao, M Carola Zillikens, Ingrid B Borecki, Ruth J F Loos, Pierre Meneton, Patrik K E Magnusson, David M Nathan, Gordon H Williams, Kaisa Silander, Veikko Salomaa, George Davey Smith, Stefan R Bornstein, Peter Schwarz, Joachim Spranger, Fredrik Karpe, Alan R Shuldiner, Cyrus Cooper, George V Dedoussis, Manuel Serrano-Ríos, Lars Lind, Lyle J Palmer, Paul W Franks, Shah Ebrahim, Michael Marmot, W H Linda Kao, Peter Paul Pramstaller, Alan F Wright, Michael Stumvoll, Anders Hamsten, Thomas A Buchanan, Timo T Valle, Jerome I Rotter, David S Siscovick, Brenda W J H Penninx, Dorret I Boomsma, Panos Deloukas, Timothy D Spector, Luigi Ferrucci, Antonio Cao, Angelo Scuteri, David Schlessinger, Manuela Uda, Aimo Ruokonen, Marjo-Riitta Jarvelin, Dawn M Waterworth, Peter Vollenweider, Leena Peltonen, Vincent Mooser, and Robert Sladek
Subjects: Medicine, Science
Abstract: African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P
Published: 2012
Full Text: View/download PDF

59. A genome-wide screen for interactions reveals a new locus on 4p15 modifying the effect of waist-to-hip ratio on total cholesterol.

Author: Ida Surakka, Aaron Isaacs, Lennart C Karssen, Pirkka-Pekka P Laurila, Rita P S Middelberg, Emmi Tikkanen, Janina S Ried, Claudia Lamina, Massimo Mangino, Wilmar Igl, Jouke-Jan Hottenga, Vasiliki Lagou, Pim van der Harst, Irene Mateo Leach, Tõnu Esko, Zoltán Kutalik, Nicholas W Wainwright, Maksim V Struchalin, Antti-Pekka Sarin, Antti J Kangas, Jorma S Viikari, Markus Perola, Taina Rantanen, Ann-Kristin Petersen, Pasi Soininen, Asa Johansson, Nicole Soranzo, Andrew C Heath, Theodore Papamarkou, Inga Prokopenko, Anke Tönjes, Florian Kronenberg, Angela Döring, Fernando Rivadeneira, Grant W Montgomery, John B Whitfield, Mika Kähönen, Terho Lehtimäki, Nelson B Freimer, Gonneke Willemsen, Eco J C de Geus, Aarno Palotie, Manj S Sandhu, Dawn M Waterworth, Andres Metspalu, Michael Stumvoll, André G Uitterlinden, Antti Jula, Gerjan Navis, Cisca Wijmenga, Bruce H R Wolffenbuttel, Marja-Riitta Taskinen, Mika Ala-Korpela, Jaakko Kaprio, Kirsten O Kyvik, Dorret I Boomsma, Nancy L Pedersen, Ulf Gyllensten, James F Wilson, Igor Rudan, Harry Campbell, Peter P Pramstaller, Tim D Spector, Jacqueline C M Witteman, Johan G Eriksson, Veikko Salomaa, Ben A Oostra, Olli T Raitakari, H-Erich Wichmann, Christian Gieger, Marjo-Riitta Järvelin, Nicholas G Martin, Albert Hofman, Mark I McCarthy, Leena Peltonen, Cornelia M van Duijn, Yurii S Aulchenko, Samuli Ripatti, and ENGAGE Consortium
Subjects: Genetics, QH426-470
Abstract: Recent genome-wide association (GWA) studies described 95 loci controlling serum lipid levels. These common variants explain ∼25% of the heritability of the phenotypes. To date, no unbiased screen for gene-environment interactions for circulating lipids has been reported. We screened for variants that modify the relationship between known epidemiological risk factors and circulating lipid levels in a meta-analysis of genome-wide association (GWA) data from 18 population-based cohorts with European ancestry (maximum N = 32,225). We collected 8 further cohorts (N = 17,102) for replication, and rs6448771 on 4p15 demonstrated genome-wide significant interaction with waist-to-hip-ratio (WHR) on total cholesterol (TC) with a combined P-value of 4.79×10(-9). There were two potential candidate genes in the region, PCDH7 and CCKAR, with differential expression levels for rs6448771 genotypes in adipose tissue. The effect of WHR on TC was strongest for individuals carrying two copies of G allele, for whom a one standard deviation (sd) difference in WHR corresponds to 0.19 sd difference in TC concentration, while for A allele homozygous the difference was 0.12 sd. Our findings may open up possibilities for targeted intervention strategies for people characterized by specific genomic profiles. However, more refined measures of both body-fat distribution and metabolic measures are needed to understand how their joint dynamics are modified by the newly found locus.
Published: 2011
Full Text: View/download PDF

60. Genetic epidemiology of attention deficit hyperactivity disorder (ADHD index) in adults.

Author: Dorret I Boomsma, Viatcheslav Saviouk, Jouke-Jan Hottenga, Marijn A Distel, Marleen H M de Moor, Jacqueline M Vink, Lot M Geels, Jenny H D A van Beek, Meike Bartels, Eco J C de Geus, and Gonneke Willemsen
Subjects: Medicine, Science
Abstract: CONTEXT: In contrast to the large number of studies in children, there is little information on the contribution of genetic factors to Attention Deficit Hyperactivity Disorder (ADHD) in adults. OBJECTIVE: To estimate the heritability of ADHD in adults as assessed by the ADHD index scored from the CAARS (Conners' Adult ADHD Rating Scales). DESIGN: Phenotype data from over 12,000 adults (twins, siblings and parents) registered with the Netherlands Twin Register were analyzed using genetic structural equation modeling. MAIN OUTCOME MEASURES: Heritability estimates for ADHD from the twin-family study. RESULTS: Heritability of ADHD in adults is estimated around 30% in men and women. There is some evidence for assortative mating. All familial transmission is explained by genetic inheritance, there is no support for the hypothesis that cultural transmission from parents to offspring is important. CONCLUSION: Heritability for ADHD features in adults is present, but is substantially lower than it is in children.
Published: 2010
Full Text: View/download PDF

61. Familial resemblance of borderline personality disorder features: genetic or cultural transmission?

Author: Marijn A Distel, Irene Rebollo-Mesa, Gonneke Willemsen, Catherine A Derom, Timothy J Trull, Nicholas G Martin, and Dorret I Boomsma
Subjects: Medicine, Science
Abstract: Borderline personality disorder is a severe personality disorder for which genetic research has been limited to family studies and classical twin studies. These studies indicate that genetic effects explain 35 to 45% of the variance in borderline personality disorder and borderline personality features. However, effects of non-additive (dominance) genetic factors, non-random mating and cultural transmission have generally not been explored. In the present study an extended twin-family design was applied to self-report data of twins (N = 5,017) and their siblings (N = 1,266), parents (N = 3,064) and spouses (N = 939) from 4,015 families, to estimate the effects of additive and non-additive genetic and environmental factors, cultural transmission and non-random mating on individual differences in borderline personality features. Results showed that resemblance among biological relatives could completely be attributed to genetic effects. Variation in borderline personality features was explained by additive genetic (21%; 95% CI 17-26%) and dominant genetic (24%; 95% CI 17-31%) factors. Environmental influences (55%; 95% CI 51-60%) explained the remaining variance. Significant resemblance between spouses was observed, which was best explained by phenotypic assortative mating, but it had only a small effect on the genetic variance (1% of the total variance). There was no effect of cultural transmission from parents to offspring.
Published: 2009
Full Text: View/download PDF

62. Combined genome scans for body stature in 6,602 European twins: evidence for common Caucasian loci.

Author: Markus Perola, Sampo Sammalisto, Tero Hiekkalinna, Nick G Martin, Peter M Visscher, Grant W Montgomery, Beben Benyamin, Jennifer R Harris, Dorret Boomsma, Gonneke Willemsen, Jouke-Jan Hottenga, Kaare Christensen, Kirsten Ohm Kyvik, Thorkild I A Sørensen, Nancy L Pedersen, Patrik K E Magnusson, Tim D Spector, Elisabeth Widen, Karri Silventoinen, Jaakko Kaprio, Aarno Palotie, Leena Peltonen, and GenomEUtwin Project
Subjects: Genetics, QH426-470
Abstract: Twin cohorts provide a unique advantage for investigations of the role of genetics and environment in the etiology of variation in common complex traits by reducing the variance due to environment, age, and cohort differences. The GenomEUtwin (http://www.genomeutwin.org) consortium consists of eight twin cohorts (Australian, Danish, Dutch, Finnish, Italian, Norwegian, Swedish, and United Kingdom) with the total resource of hundreds of thousands of twin pairs. We performed quantitative trait locus (QTL) analysis of one of the most heritable human complex traits, adult stature (body height) using genome-wide scans performed for 3,817 families (8,450 individuals) derived from twin cohorts from Australia, Denmark, Finland, Netherlands, Sweden, and United Kingdom with an approximate ten-centimorgan microsatellite marker map. The marker maps for different studies differed and they were combined and related to the sequence positions using software developed by us, which is publicly available (https://apps.bioinfo.helsinki.fi/software/cartographer.aspx). Variance component linkage analysis was performed with age, sex, and country of origin as covariates. The covariate adjusted heritability was 81% for stature in the pooled dataset. We found evidence for a major QTL for human stature on 8q21.3 (multipoint logarithm of the odds 3.28), and suggestive evidence for loci on Chromosomes X, 7, and 20. Some evidence of sex heterogeneity was found, however, no obvious female-specific QTLs emerged. Several cohorts contributed to the identified loci, suggesting an evolutionarily old genetic variant having effects on stature in European-based populations. To facilitate the genetic studies of stature we have also set up a website that lists all stature genome scans published and their most significant loci (http://www.genomeutwin.org/stature_gene_map.htm).
Published: 2007
Full Text: View/download PDF

63. DNA Methylation Signatures of Educational Attainment

Author: Jenny van Dongen, Marc Jan Bonder, Koen F. Dekkers, Michel G. Nivard, Maarten van Iterson, Gonneke Willemsen, Marian Beekman, Ashley van der Spek, Joyce B. J. van Meurs, Lude Franke, Bastiaan T. Heijmans, Cornelia M. van Duijn, P. Eline Slagboom, Dorret I. Boomsma, and BIOS Consortium
Abstract: Educational attainment is a key behavioural measure in studies of cognitive and physical health, and socioeconomic status. We measured DNA methylation at 410,746 CpGs (N = 4152) and identified 58 CpGs associated with educational attainment at loci characterized by pleiotropic functions shared with neuronal, immune and developmental processes. Associations overlapped with those for smoking behaviour, but remained after accounting for smoking at many CpGs: Effect sizes were on average 28% smaller and genome-wide significant at 11 CpGs after adjusting for smoking and were 62% smaller in never smokers. We examined sources and biological implications of education-related methylation differences, demonstrating correlations with maternal prenatal folate, smoking and air pollution signatures, and associations with gene expression in cis, dynamic methylation in foetal brain, and correlations between blood and brain. Our findings show that the methylome of lower-educated people resembles that of smokers beyond effects of their own smoking behaviour and shows traces of various other exposures.
Published: 2018
Full Text: View/download PDF

64. DNA methylation analysis is used to identify novel genetic loci associated with circulating fibrinogen levels in blood

Author: Julie Hahn, Jan Bressler, Arce Domingo-Relloso, Ming-Huei Chen, Daniel L. McCartney, Alexander Teumer, Jenny van Dongen, Marcus E. Kleber, Dylan Aïssi, Brenton R. Swenson, Jie Yao, Wei Zhao, Jian Huang, Yujing Xia, Michael R. Brown, Ricardo Costeira, Eco J.C. de Geus, Graciela E. Delgado, Dre'Von A. Dobson, Paul Elliott, Hans J. Grabe, Xiuqing Guo, Sarah E. Harris, Jennifer E. Huffman, Sharon L.R. Kardia, Yongmei Liu, Stefan Lorkowski, Riccardo E. Marioni, Matthias Nauck, Scott M. Ratliff, Maria Sabater-Lleal, Tim D. Spector, Pierre Suchon, Kent D. Taylor, Florian Thibord, David-Alexandre Trégouët, Kerri L. Wiggins, Gonneke Willemsen, Jordana T. Bell, Dorret I. Boomsma, Shelley A. Cole, Simon R. Cox, Abbas Dehghan, Andreas Greinacher, Karin Haack, Winfried März, Pierre-Emmanuel Morange, Jerome I. Rotter, Nona Sotoodehnia, Maria Tellez-Plaza, Ana Navas-Acien, Jennifer A. Smith, Andrew D. Johnson, Myriam Fornage, Nicholas L. Smith, Alisa S. Wolberg, Alanna C. Morrison, Paul S. de Vries, Biological Psychology, Amsterdam Reproduction & Development, APH - Mental Health, APH - Personalized Medicine, AMS - Ageing & Vitality, AMS - Sports, APH - Health Behaviors & Chronic Diseases, and APH - Methodology
Subjects: DNA methylation, Hematology, genetics [Fibrinogen], methods [Genome-Wide Association Study], epigenome-wide association study, Epigenesis, Genetic, genetics [Inflammation], SDG 3 - Good Health and Well-being, Genetic Loci, inflammation, Mendelian randomization, Humans, CpG Islands, ddc:610, fibrinogen
Abstract: Background: Fibrinogen plays an essential role in blood coagulation and inflammation. Circulating fibrinogen levels may be determined based on interindividual differences in DNA methylation at cytosine-phosphate-guanine (CpG) sites and vice versa. Objectives: To perform an EWAS to examine an association between blood DNA methylation levels and circulating fibrinogen levels to better understand its biological and pathophysiological actions. Methods: We performed an epigenome-wide association study of circulating fibrinogen levels in 18 037 White, Black, American Indian, and Hispanic participants, representing 14 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium. Circulating leukocyte DNA methylation was measured using the Illumina 450K array in 12 904 participants and using the EPIC array in 5133 participants. In each study, an epigenome-wide association study of fibrinogen was performed using linear mixed models adjusted for potential confounders. Study-specific results were combined using array-specific meta-analysis, followed by cross-replication of epigenome-wide significant associations. We compared models with and without CRP adjustment to examine the role of inflammation. Results: We identified 208 and 87 significant CpG sites associated with fibrinogen levels from the 450K (p < 1.03 × 10−7) and EPIC arrays (p < 5.78 × 10−8), respectively. There were 78 associations from the 450K array that replicated in the EPIC array and 26 vice versa. After accounting for overlapping sites, there were 83 replicated CpG sites located in 61 loci, of which only 4 have been previously reported for fibrinogen. The examples of genes located near these CpG sites were SOCS3 and AIM2, which are involved in inflammatory pathways. The associations of all 83 replicated CpG sites were attenuated after CRP adjustment, although many remained significant. Conclusion: We identified 83 CpG sites associated with circulating fibrinogen levels. These associations are partially driven by inflammatory pathways shared by both fibrinogen and CRP.
Published: 2023
Full Text: View/download PDF

65. Changing genetic architecture of body mass index from infancy to early adulthood

Author: Karri Silventoinen, Weilong Li, Aline Jelenkovic, Reijo Sund, Yoshie Yokoyama, Sari Aaltonen, Maarit Piirtola, Masumi Sugawara, Mami Tanaka, Satoko Matsumoto, Laura A. Baker, Catherine Tuvblad, Per Tynelius, Finn Rasmussen, Jeffrey M. Craig, Richard Saffery, Gonneke Willemsen, Meike Bartels, Catharina E. M. van Beijsterveldt, Nicholas G. Martin, Sarah E. Medland, Grant W. Montgomery, Paul Lichtenstein, Robert F. Krueger, Matt McGue, Shandell Pahlen, Kaare Christensen, Axel Skytthe, Kirsten O. Kyvik, Kimberly J. Saudino, Lise Dubois, Michel Boivin, Mara Brendgen, Ginette Dionne, Frank Vitaro, Vilhelmina Ullemar, Catarina Almqvist, Patrik K. E. Magnusson, Robin P. Corley, Brooke M. Huibregtse, Ariel Knafo-Noam, David Mankuta, Lior Abramson, Claire M. A. Haworth, Robert Plomin, Morten Bjerregaard-Andersen, Henning Beck-Nielsen, Morten Sodemann, Glen E. Duncan, Dedra Buchwald, S. Alexandra Burt, Kelly L. Klump, Clare H. Llewellyn, Abigail Fisher, Dorret I. Boomsma, Thorkild I. A. Sørensen, Jaakko Kaprio, Helsinki Inequality Initiative (INEQ), Demography, Population Research Unit (PRU), Center for Population, Health and Society, Sociology, University of Helsinki, Clinicum, Department of Physiology, Department of Public Health, Faculty Common Matters (Faculty of Social Sciences), Institute for Molecular Medicine Finland, Technology Centre, Genetic Epidemiology, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, APH - Personalized Medicine, Amsterdam Reproduction & Development, and APH - Methodology
Subjects: COLLABORATIVE PROJECT, Adult, Adolescent, Endocrinology, Diabetes and Metabolism, CHILDHOOD, Medicine (miscellaneous), Body Mass Index, BMI, Young Adult, AGE, HEIGHT, SDG 3 - Good Health and Well-being, ENVIRONMENTAL VARIATION, Twins, Dizygotic, Humans, Obesity, Child, METABOLIC SYNDROME, Nutrition and Dietetics, ANTHROPOMETRICAL MEASURES, Infant, Twins, Monozygotic, Body Height, 3141 Health care science, OBESITY, Child, Preschool, WEIGHT
Abstract: Background Body mass index (BMI) shows strong continuity over childhood and adolescence and high childhood BMI is the strongest predictor of adult obesity. Genetic factors strongly contribute to this continuity, but it is still poorly known how their contribution changes over childhood and adolescence. Thus, we used the genetic twin design to estimate the genetic correlations of BMI from infancy to adulthood and compared them to the genetic correlations of height. Methods We pooled individual level data from 25 longitudinal twin cohorts including 38,530 complete twin pairs and having 283,766 longitudinal height and weight measures. The data were analyzed using Cholesky decomposition offering genetic and environmental correlations of BMI and height between all age combinations from 1 to 19 years of age. Results The genetic correlations of BMI and height were stronger than the trait correlations. For BMI, we found that genetic correlations decreased as the age between the assessments increased, a trend that was especially visible from early to middle childhood. In contrast, for height, the genetic correlations were strong between all ages. Age-to-age correlations between environmental factors shared by co-twins were found for BMI in early childhood but disappeared altogether by middle childhood. For height, shared environmental correlations persisted from infancy to adulthood. Conclusions Our results suggest that the genes affecting BMI change over childhood and adolescence leading to decreasing age-to-age genetic correlations. This change is especially visible from early to middle childhood indicating that new genetic factors start to affect BMI in middle childhood. Identifying mediating pathways of these genetic factors can open possibilities for interventions, especially for those children with high genetic predisposition to adult obesity. This study was conducted within the CODATwins project. Support for collaborators: Colorado Twin Registry is funded by NIDA funded center grant DA011015, & Longititudinal Twin Study HD10333; Author Huibregtse is supported by National Institute on Drug Abuse (5T32DA017637) and National Institute on Aging (5T32AG052371). Finnish Twin Cohort is supported by the Academy of Finland (grants 312073 and 336823) and the Sigrid Juselius Foundation. Michigan State University Twin Registry was supported by National Institute of Mental Health (NIMH) (R01-MH081813, R01-MH0820–54, R01-MH092377-02, R21-MH070542-01, R03-MH63851-01, 1R01-MH118848-01), Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD) (R01-HD066040) and MSU Foundation (11-SPG-2518). PETS was funded by the Australian National Health and Medical Research Council (grant numbers 437015 and 607358); the Bonnie Babes Foundation (grant number BBF20704); the Financial Markets Foundation for Children (grant number 032-2007); and the Victorian Government’s Operational Infrastructure Support Program. We acknowledge The Swedish Twin Registry for access to data. The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council under the grant no 2017-00641. TEDS was supported by a program grant to RP from the UK Medical Research Council (MR/M021475/1 and previously G0901245), with additional support from the US National Institutes of Health (AG046938). The West Japan Twins and Higher Order Multiple Births Registry was supported by Grant-in-Aid for Scientific Research (B) (grant number 20H04019) from the Japan Society for the Promotion of Science. Open Access funding provided by University of Helsinki including Helsinki University Central Hospital.
Published: 2022
Full Text: View/download PDF

66. Polygenic Score for Dizygotic Twinning in Mothers of Spontaneously and Artificially Conceived Twins and Singletons

Author: Nikki Hubers, Christian Page, Hamdi Mbarek, Nils Lambalk, Lannie Ligthart, Rene Pool, Hottenga Jouke Jan, Dongen Jenny van, Siri Haberg, Erik Ehli, Jennifer Harris, Gonneke Willemsen, and Dorret Boomsma
Subjects: General Medicine
Published: 2023
Full Text: View/download PDF

67. Direct and Indirect Genetic Effects on Aggression

Author: Camiel M. van der Laan, Steve G.A. van de Weijer, René Pool, Jouke-Jan Hottenga, Toos C.E.M. van Beijsterveldt, Gonneke Willemsen, Meike Bartels, Michel G. Nivard, and Dorret I. Boomsma
Subjects: General Medicine
Published: 2023
Full Text: View/download PDF

68. Sociodemographic, lifestyle and clinical characteristics of energy-related depression symptoms:A pooled analysis of 13,965 depressed cases in 8 Dutch cohorts

Author: Sarah R. Vreijling, Marije van Haeringen, Yuri Milaneschi, Floris Huider, Mariska Bot, Najaf Amin, Joline W. Beulens, Marijke A. Bremmer, Petra J. Elders, Tessel E. Galesloot, Lambertus A. Kiemeney, Hanna M. van Loo, H. Susan J. Picavet, Femke Rutters, Ashley van der Spek, Anne M. van de Wiel, Cornelia van Duijn, Edith J.M. Feskens, Catharina A. Hartman, Albertine J. Oldehinkel, Jan H. Smit, W.M. Monique Verschuren, Gonneke Willemsen, Eco J.C. de Geus, Dorret I. Boomsma, Brenda W.J.H. Penninx, Femke Lamers, Rick Jansen, Biological Psychology, APH - Mental Health, APH - Methodology, APH - Health Behaviors & Chronic Diseases, AMS - Sports, AMS - Ageing & Vitality, APH - Personalized Medicine, Amsterdam Reproduction & Development, Sociology and Social Gerontology, Clinical Psychology, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Epidemiology and Data Science, ACS - Diabetes & metabolism, ACS - Heart failure & arrhythmias, APH - Aging & Later Life, General practice, APH - Digital Health, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), and Epidemiology
Subjects: Global Nutrition, Wereldvoeding, Psychiatry and Mental health, Clinical Psychology, All institutes and research themes of the Radboud University Medical Center, Clinical characteristics, SDG 3 - Good Health and Well-being, Depression, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Depression symptoms, HNRU&LB, VLAG
Abstract: BACKGROUND: In a substantial subgroup of depressed patients, atypical, energy-related depression symptoms (e.g. increased appetite/weight, hypersomnia, loss of energy) tend to cluster with immuno-metabolic dysregulations (e.g. increased BMI and inflammatory markers). This clustering is proposed to reflect a more homogeneous depression pathology. This study examines to what extent energy-related symptoms are associated and share sociodemographic, lifestyle and clinical characteristics.METHODS: Data were available from 13,965 participants from eight Dutch cohorts with DSM-5 lifetime major depression assessed by the Lifetime Depression Assessment Self-report (LIDAS) questionnaire. Information on four energy-related depression symptoms were extracted: energy loss, increased appetite, increased weight, and hypersomnia. Tetrachoric correlations between these symptoms, and associations of these symptoms with sociodemographic (sex, age, education), lifestyle (physical activity, BMI, smoking) and clinical characteristics (age of onset, episode duration, history, treatment and recency, and self-reported comorbidity) were computed.RESULTS: Correlations between energy-related symptoms were overall higher than those with other depression symptoms and varied from 0.90 (increased appetite vs increased weight) to 0.11 (increased appetite vs energy loss). All energy-related symptoms were strongly associated with higher BMI and a more severe clinical profile. Patients with increased appetite were more often smokers, and only patients with increased appetite or weight more often had a self-reported diagnosis of PTSD (OR = 1.17, p = 2.91E-08) and eating disorder (OR = 1.40, p = 4.08E-17).CONCLUSIONS: The symptom-specific associations may have consequences for a profile integrating these symptoms, which can be used to reflect immuno-metabolic depression. They indicate the need to study immuno-metabolic depression at individual symptom resolution as a starting point.
Published: 2023
Full Text: View/download PDF

69. Plasma biomarkers predict amyloid pathology in cognitively normal monozygotic twins after 10 years

Author: Anouk den Braber, Inge M W Verberk, Jori Tomassen, Ben den Dulk, Erik Stoops, Jeffrey L Dage, Lyduine E Collij, Frederik Barkhof, Gonneke Willemsen, Michel G Nivard, Bart N M van Berckel, Philip Scheltens, Pieter Jelle Visser, Eco J C de Geus, Charlotte E Teunissen, Neurology, Amsterdam Neuroscience - Neurodegeneration, Neurochemistry Laboratory, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Neuroinfection & -inflammation, CCA - Cancer Treatment and quality of life, CCA - Imaging and biomarkers, Biological Psychology, VUmc - School of Medical Sciences, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, APH - Methodology, AMS - Sports, AMS - Ageing & Vitality, APH - Personalized Medicine, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, and Psychology 6
Subjects: PLAQUES, BETA, PERFORMANCE, confounding, ALZHEIMERS-DISEASE, Cellular and Molecular Neuroscience, Psychiatry and Mental health, monozygotic twins, plasma biomarkers, Neurology, amyloid pathology, TAU, Biological Psychiatry, longitudinal dynamics
Abstract: den Braber et al. report that plasma levels of amyloid-beta(1-42/1-40), p-tau181 and GFAP can be used to predict amyloid-beta pathology in older cognitively unimpaired individuals, as long as 10 years before the presence of amyloid-beta pathology, indicating the potential of these markers as early diagnostic tools in the normal aging population.Blood-based biomarkers could prove useful to predict Alzheimer's disease core pathologies in advance of clinical symptoms. Implementation of such biomarkers requires a solid understanding of their long-term dynamics and the contribution of confounding to their association with Alzheimer's disease pathology. Here we assess the value of plasma amyloid-beta(1-42/1-40), phosphorylated-tau181 and glial fibrillary acidic protein to detect early Alzheimer's disease pathology, accounting for confounding by genetic and early environmental factors. Participants were 200 monozygotic twins, aged >= 60 years with normal cognition from the european medical information framework for Alzheimer's disease study. All twins had amyloid-beta status and plasma samples available at study enrolment. For 80 twins, additional plasma samples were available that had been collected approximately 10 years prior to amyloid-beta status assessment. Single-molecule array assays were applied to measure amyloid-beta(1-42/1-40), phosphorylated-tau181 and glial fibrillary acidic protein. Predictive value of and longitudinal change in these biomarkers were assessed using receiver operating characteristic curve analysis and linear mixed models. Amyloid pathology could be predicted using blood-based biomarkers obtained at the time of amyloid status assessment (amyloid-beta(1-42/1-40): area under the curve = 0.65, P = 0.01; phosphorylated-tau181: area under the curve = 0.84, P < 0.001; glial fibrillary acidic protein: area under the curve = 0.74, P < 0.001), as well as using those obtained 10 years prior to amyloid status assessment (amyloid-beta(1-42/1-40): area under the curve = 0.69, P = 0.03; phosphorylated-tau181: area under the curve = 0.92, P < 0.001; glial fibrillary acidic protein: area under the curve = 0.84, P < 0.001). Longitudinally, amyloid-beta(1-42/1-40) levels decreased [beta (SE) = -0.12 (0.01), P < 0.001] and phosphorylated-tau181 levels increased [beta (SE) = 0.02 (0.01), P = 0.004]. Amyloid-beta-positive individuals showed a steeper increase in phosphorylated-tau181 compared with amyloid-beta-negative individuals [beta (SE) = 0.06 (0.02), P = 0.004]. Also amyloid-beta-positive individuals tended to show a steeper increase in glial fibrillary acidic protein [beta (SE) = 0.04 (0.02), P = 0.07]. Within monozygotic twin pairs, those with higher plasma phosphorylated-tau181 and lower amyloid-beta(1-42/1-40) levels were more likely to be amyloid-beta positive [beta (SE) = 0.95 (0.26), P < 0.001; beta (SE) = -0.28 (0.14), P < 0.05] indicating minimal contribution of confounding by genetic and early environmental factors. Our data support the use of amyloid-beta(1-42/1-40), phosphorylated-tau181 and glial fibrillary acidic protein as screening tools for Alzheimer's disease pathology in the normal aging population, which is of importance for enrolment of high-risk subjects in secondary, or even primary, prevention trials. Furthermore, these markers show potential as low-invasive monitoring tool of disease progression and possibly treatment effects in clinical trials.
Published: 2023
Full Text: View/download PDF

70. The heritability of pescetarianism and vegetarianism

Author: Laura W. Wesseldijk, Joshua M. Tybur, Dorret I. Boomsma, Gonneke Willemsen, Jacqueline M. Vink, Social Psychology, IBBA, Biological Psychology, Amsterdam Reproduction & Development, APH - Mental Health, and APH - Methodology
Subjects: Nutrition and Dietetics, Developmental Psychopathology, Food Science
Abstract: Contains fulltext : 282337.pdf (Publisher’s version ) (Open Access) Genetic factors have a substantial influence on individuals' food preferences, but less is known about their influence on abstinence from eating meat and fish. Here we looked at the influence genetics may have on pescetarianism (not eating meat but eating fish) and vegetarianism (not eating meat and fish) in a Dutch twin sample (N = 8196). We also examined genetic and environmental influences on abstinence from eating beef, pork, poultry, fish or shellfish separately and explored the reasons individuals gave for not eating these types of meat and fish (e.g., disliking, health concerns or beliefs). Abstinence from eating various meats or (shell)fish varied from 5.3% for beef to 46% for shellfish, and 3.7% did not eat meat (1.9% was pescatarian and 1.8% vegetarian). The prevalence of all abstinences was higher in women than men. Genetic factors accounted for 74% and 77% of variation in pescetarianism and vegetarianism, respectively, with the remaining variance accounted for by non-shared environmental influences. Heritability for abstinence from eating beef, pork, poultry, fish or shellfish ranged from 70 to 80%. Abstention from pork was mostly due to health concerns, abstention from poultry, fish and shellfish because of dislike, and abstention from beef because of beliefs (i.e., religion or convictions). Most pescatarians and vegetarians reported beliefs as one of their reason for abstinence (∼75%). Overall, regardless of the fact that different reasons seem to play a role in pescetarianism, vegetarianism and abstinence from eating different meats and fish, genetic factors undergirded all with a similar large magnitude. 5 p.
Published: 2023
Full Text: View/download PDF

71. Value of plasma biomarkers to predict memory change in cognitively unimpaired individuals

Author: Anouk den Braber, Inge M.W. Verberk, Jori Tomassen, Emma M Coomans, Sophie M van der Landen, Lynn Boonkamp, Jeffrey L. Dage, Erik Stoops, Gonneke Willemsen, Michel G. Nivard, Bart NM van Berckel, Philip Scheltens, Pieter Jelle Visser, Eco J.C. de Geus, and Charlotte E. Teunissen
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published: 2022
Full Text: View/download PDF

72. Educational attainment of same-sex and opposite-sex dizygotic twins

Author: Glen E. Duncan, Juan R. Ordoñana, Aline Jelenkovic, Esther Rebato, Amie E. Hwang, Wendy Cozen, Zengchang Pang, Weilong Li, Matthew Hotopf, Sisira Siribaddana, Leonie Helen Bogl, Dedra Buchwald, Robert F. Krueger, Brooke M. Huibregtse, Dorret I. Boomsma, Karri Silventoinen, Catherine Derom, Meike Bartels, Lucía Colodro-Conde, Ruth J. F. Loos, Catharina E. M. van Beijsterveldt, Athula Sumathipala, Jessica Tyler, Sarah E. Medland, Nicholas G. Martin, Fruhling Rijsdijk, Robert Vlietinck, Shandell Pahlen, Tracy L. Nelson, Kauko Heikkilä, Richard J. Rose, Anna K. Dahl Aslan, Thorkild I. A. Sørensen, Virgilia Toccaceli, Patrik K. E. Magnusson, Judy L. Silberg, John L. Hopper, Thomas M. Mack, Emanuela Medda, Grant W. Montgomery, Antti Latvala, Juan F. Sánchez-Romera, Qihua Tan, Dongfeng Zhang, Gonneke Willemsen, Matt McGue, Nancy L. Pedersen, Keith E. Whitfield, Jaakko Kaprio, Eero Vuoksimaa, Lorenza Nisticò, Christian Kandler, Hermine H. Maes, Robin P. Corley, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, APH - Personalized Medicine, APH - Methodology, Helsinki Inequality Initiative (INEQ), Demography, Population Research Unit (PRU), Center for Population, Health and Society, Sociology, Department of Social Research (2010-2017), Institute for Molecular Medicine Finland, Clinicum, Department of Physiology, Department of Public Health, Cognitive and Brain Aging, Faculty Common Matters (Faculty of Medicine), Institute of Criminology and Legal Policy, Faculty Common Matters (Faculty of Education), and Technology Centre
Subjects: Male, Twins, Dizygotic twins, Education, Cohort Studies, 03 medical and health sciences, Behavioral Neuroscience, 0302 clinical medicine, Endocrinology, 5. Gender equality, Sex differences in education, RA0421, Twins, Dizygotic, Humans, Medicine, Testosterone, 10. No inequality, Birth Year, Medicinsk genetik, 030304 developmental biology, Sex Characteristics, 0303 health sciences, Psykologi (exklusive tillämpad psykologi), Endocrine and Autonomic Systems, business.industry, Public Health, Global Health, Social Medicine and Epidemiology, Testosterone (patch), Twin study, Testosterone exposure, Confidence interval, Educational attainment, Psychology (excluding Applied Psychology), Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, 5141 Sociology, Cohort, Educational Status, 1182 Biochemistry, cell and molecular biology, Female, business, Medical Genetics, RA, Twin testosterone transfer hypothesis, SDG 4 - Quality Education, 030217 neurology & neurosurgery, Demography
Abstract: Comparing twins from same- and opposite-sex pairs can provide information on potential sex differences in a variety of outcomes, including socioeconomic-related outcomes such as educational attainment. It has been suggested that this design can be applied to examine the putative role of intrauterine exposure to testosterone for educational attainment, but the evidence is still disputed. Thus, we established an international database of twin data from 11 countries with 88,290 individual dizygotic twins born over 100 years and tested for differences between twins from same- and opposite-sex dizygotic pairs in educational attainment. Effect sizes with 95% confidence intervals (CI) were estimated by linear regression models after adjusting for birth year and twin study cohort. In contrast to the hypothesis, no difference was found in women (β = −0.05 educational years, 95% CI −0.11, 0.02). However, men with a same-sex co-twin were slightly more educated than men having an opposite-sex co-twin (β = 0.14 educational years, 95% CI 0.07, 0.21). No consistent differences in effect sizes were found between individual twin study cohorts representing Europe, the USA, and Australia or over the cohorts born during the 20th century, during which period the sex differences in education reversed favoring women in the latest birth cohorts. Further, no interaction was found with maternal or paternal education. Our results contradict the hypothesis that there would be differences in the intrauterine testosterone levels between same-sex and opposite-sex female twins affecting education. Our findings in men may point to social dynamics within same-sex twin pairs that may benefit men in their educational careers. CC BY 4.0Correspondence Address: Silventoinen, K.; University of Helsinki, P.O. Box 18, Finland; email: karri.silventoinen@helsinki.fi© 2021 The Authors
Published: 2021
Full Text: View/download PDF

73. Male microchimerism in females

Author: Henrike E. Peters, B N Johnson, Gonneke Willemsen, J-J Hottenga, Lannie Ligthart, Dorret I. Boomsma, Velja Mijatovic, Conor V. Dolan, C.B. Lambalk, E.A. Ehli, Obstetrics and gynaecology, Amsterdam Reproduction & Development (AR&D), ACS - Atherosclerosis & ischemic syndromes, Biological Psychology, APH - Methodology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, and APH - Personalized Medicine
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Offspring, Placenta, Population, Physiology, Pedigree chart, 030230 surgery, 03 medical and health sciences, Human reproduction, 0302 clinical medicine, monozygotic twins, SDG 3 - Good Health and Well-being, Pregnancy, Epidemiology, medicine, microchimerism, Humans, dizygotic twins, education, Biological Specimen Banks, education.field_of_study, Reproductive Biology, business.industry, Rehabilitation, Obstetrics and Gynecology, pedigree, Microchimerism, Odds ratio, Original Articles, twins, medicine.disease, AcademicSubjects/MED00905, United States, 030104 developmental biology, Cross-Sectional Studies, female, Reproductive Medicine, chimerism, business
Abstract: STUDY QUESTION Does having a male co-twin, older brothers, or sons lead to an increased probability of persistent male microchimerism in female members of twin pedigrees? SUMMARY ANSWER The presence of a male co-twin did not increase risk of male microchimerism and the prevalence of male microchimerism was not explained by having male offspring or by having an older brother. WHAT IS KNOWN ALREADY Microchimerism describes the presence of cells within an organism that originate from another zygote and is commonly described as resulting from pregnancy in placental mammals. It is associated with diseases with a female predilection including autoimmune diseases and pregnancy-related complications. However, microchimerism also occurs in nulliparous women; signifying gaps in the understanding of risk factors contributing to persistent microchimerism and the origin of the minor cell population. STUDY DESIGN, SIZE, DURATION This cross-sectional study composed of 446 adult female participants of the Netherlands Twin Register (NTR). PARTICIPANTS/MATERIALS, SETTING, METHODS Participants included in the study were female monozygotic (MZ) twins, female dizygotic same-sex twins and females of dizygotic opposite-sex twin pairs, along with the mothers and sisters of these twins. Peripheral blood samples collected from adult female participants underwent DNA extraction and were biobanked prior to the study. To detect the presence of male-origin microchimerism, DNA samples were tested for the relative quantity of male specific Y chromosome gene DYS14 compared to a common β-globin gene using a highly sensitive quantitative PCR assay. MAIN RESULTS AND THE ROLE OF CHANCE We observed a large number of women (26.9%) having detectable male microchimerism in their peripheral blood samples. The presence of a male co-twin did not increase risk of male microchimerism (odds ratio (OR) = 1.23: SE 0.40, P = 0.61) and the prevalence of male microchimerism was not explained by having male offspring (OR 0.90: SE 0.19, P = 0.63) or by having an older brother (OR = 1.46: SE 0.32, P = 0.09). The resemblance (correlation) for the presence of microchimerism was similar (P = 0.66) in MZ pairs (0.27; SE 0.37) and in first-degree relatives (0.091; SE 0.092). However, age had a positive relationship with the presence of male microchimerism (P = 0.02). LIMITATIONS, REASONS FOR CAUTION After stratifying for variables of interest, some participant groups resulted in a low numbers of subjects. We investigated microchimerism in peripheral blood due to the proposed mechanism of cell acquisition via transplacental blood exchange; however, this does not represent global chimerism in the individual and microchimerism may localize to numerous other tissues. WIDER IMPLICATIONS OF THE FINDINGS Immune regulation during pregnancy is known to mitigate allosensitization and support tolerance to non-inherited antigens found on donor cells. While unable to identify a specific source that promotes microchimerism prevalence within pedigrees, this study points to the underlying complexities of natural microchimerism in the general population. These findings support previous studies which have identified the presence of male microchimerism among women with no history of pregnancy, suggesting alternative sources of microchimerism. The association of detectable male microchimerism with age is suggestive of additional factors including time, molecular characteristics and environment playing a critical role in the prevalence of persistent microchimerism. The present study necessitates investigation into the molecular underpinnings of natural chimerism to provide insight into women’s health, transplant medicine and immunology. STUDY FUNDING/COMPETING INTEREST(S) This work is funded by Royal Netherlands Academy of Science Professor Award (PAH/6635 to D.I.B.); The Netherlands Organisation for Health Research and Development (ZonMw)—Genotype/phenotype database for behavior genetic and genetic epidemiological studies (ZonMw 911-09-032); Biobanking and Biomolecular Research Infrastructure (BBMRI–NL, 184.021.007; 184.033.111); The Netherlands Organisation for Scientific Research (NWO)—Netherlands Twin Registry Repository (NWO-Groot 480-15-001/674); the National Institutes of Health—The Rutgers University Cell and DNA Repository cooperative agreement (NIMH U24 MH068457-06), Grand Opportunity grants Integration of genomics and transcriptomics in normal twins and major depression (NIMH 1RC2 MH089951-01), and Developmental trajectories of psychopathology (NIMH 1RC2 MH089995); and European Research Council—Genetics of Mental Illness (ERC 230374). C.B.L. declares a competing interest as editor-in-chief of Human Reproduction and his department receives unrestricted research grants from Ferring, Merck and Guerbet. All remaining authors have no conflict-of-interest to declare in regards to this work. TRIAL REGISTRATION NUMBER N/A.
Published: 2021
Full Text: View/download PDF

74. Expanding the environmental scope: an environment-wide association study for mental well-being

Author: Gonneke Willemsen, Meike Bartels, Margot P van de Weijer, Conor V. Dolan, Bart M. L. Baselmans, Jouke-Jan Hottenga, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, APH - Methodology, and APH - Mental Health
Subjects: Estimation, 0303 health sciences, education.field_of_study, Epidemiology, Population, Public Health, Environmental and Occupational Health, Public policy, Environmental exposure, Toxicology, Pollution, Mental health, SDG 11 - Sustainable Cities and Communities, 03 medical and health sciences, 0302 clinical medicine, Environmental health, education, Psychology, Neighbourhood (mathematics), Socioeconomic status, 030217 neurology & neurosurgery, Record linkage, 030304 developmental biology
Abstract: Background Identifying modifiable factors associated with well-being is of increased interest for public policy guidance. Developments in record linkage make it possible to identify what contributes to well-being from a myriad of factors. To this end, we link two large-scale data resources; the Geoscience and Health Cohort Consortium, a collection of geo-data, and the Netherlands Twin Register, which holds population-based well-being data. Objective We perform an Environment-Wide Association Study (EnWAS), where we examine 139 neighbourhood-level environmental exposures in relation to well-being. Methods First, we performed a generalized estimation equation regression (N = 11,975) to test for the effects of environmental exposures on well-being. Second, to account for multicollinearity amongst exposures, we performed principal component regression. Finally, using a genetically informative design, we examined whether environmental exposure is driven by genetic predisposition for well-being. Results We identified 21 environmental factors that were associated with well-being in the domains: housing stock, income, core neighbourhood characteristics, livability, and socioeconomic status. Of these associations, socioeconomic status and safety are indicated as the most important factors to explain differences in well-being. No evidence of gene-environment correlation was found. Significance These observed associations, especially neighbourhood safety, could be informative for policy makers and provide public policy guidance to improve well-being. Our results show that linking databases is a fruitful exercise to identify determinants of mental health that would remain unknown by a more unilateral approach.
Published: 2021
Full Text: View/download PDF

75. Self-rated health when population health is challenged by the COVID-19 pandemic; a longitudinal study

Author: Margot P. van de Weijer, Lianne P. de Vries, Dirk H.M. Pelt, Lannie Ligthart, Gonneke Willemsen, Dorret I. Boomsma, Eco de Geus, Meike Bartels, Biological Psychology, APH - Personalized Medicine, APH - Methodology, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, AMS - Ageing & Vitality, and AMS - Sports
Subjects: Health (social science), Population Health, Pandemic, Health Status, Twin study, Self-rated health, History and Philosophy of Science, SDG 3 - Good Health and Well-being, Communicable Disease Control, Lockdown, Humans, Longitudinal Studies, Covid-19, Pandemics
Abstract: Rationale: The coronavirus disease 2019 (COVID-19) pandemic and consequent lockdown measures have had a large impact on people's lives. Recent evidence suggests that self-rated health (SRH) scores remained relatively stable or increased during the pandemic. Objective: For the current project, we examine potential changes in the variance decomposition of SRH before and during the COVID-19 pandemic in the Netherlands. Methods: We analyse data from the Netherlands Twin Register to examine pre-pandemic SRH scores (N = 16,127), pandemic SRH scores (N = 17,451), and SRH difference scores (N = 7464). Additionally, we perform bivariate genetic analyses to estimate genetic and environmental variance components in pre-pandemic and pandemic SRH, and estimate the genetic correlation to assess potential gene-environment interaction. Results: The majority of the sample (66.7%) reported the same SRH before and during the pandemic, while 10.8% reported a decrease, and 22.5% an increase. Individuals who reported good/excellent SRH before the pandemic were most likely to report unchanged SRH during the pandemic, and individuals with bad/mediocre/reasonable SRH more often reported increased SRH. The bivariate longitudinal genetic model reveals no significant change in variance decomposition of SRH from before to during the pandemic, with a heritability estimate of 45% (CI 36%–52%). We found that the genetic correlation could be constrained to 1, and a moderate unique environmental correlation (rE = 0.49, CI = 0.37 to 0.60). Conclusions: We theorize that the increases in SRH are explained by uninfected individuals evaluating their health more positively than under normal circumstances (partly through social comparison with infected individuals), rather than actual improvements. As the same genes are expressed under different environmental exposures, these results imply no evidence for gene-environment interaction. While different environmental factors might influence SRH at the two time-points, the influence of environmental factors does not become relatively more important during the pandemic.
Published: 2022
Full Text: View/download PDF

76. Genome-wide association study of circulating interleukin 6 levels identifies novel loci

Author: Martina Müller-Nurasyid, Jerome I. Rotter, David M. Evans, John P. Kemp, Emelia J. Benjamin, Graciela E. Delgado, Vilmundur Gudnason, Ann Hammarstedt, Panos Deloukas, Aroon D. Hingorani, Riccardo E. Marioni, David Stacey, Jenny van Dongen, Eric Boerwinkle, Joachim Heinrich, Yongmei Liu, S. Goya Wannamethee, Delilah Zabaneh, Braxton D. Mitchell, Marie Standl, Jackie F. Price, Maria G. Stathopoulou, Yoav Ben-Shlomo, Joris Deelen, Eero Kajantie, Mohammadreza Abdollahi, Christie M. Ballantyne, Johan G. Eriksson, Ilkka Seppälä, Elnaz Naderi, Barbara J. Jefferis, Richard W Morris, Nicholas J. Timpson, George Dedoussis, Sirpa Jalkanen, Mika Kivimäki, Perminder S. Sachdev, Diana van Heemst, Melanie Waldenberger, Gaurav Singhal, Elisabeth Thiering, Olli T. Raitakari, Anders Hamsten, Zoltán Kutalik, L. Bain, Eco J. C. de Geus, Tarunveer S. Ahluwalia, Yuri Milaneschi, Hubert Scharnagl, Juan P. Casas, Georg Homuth, Claes Ohlsson, Abbas Dehghan, Nicola J. Armstrong, Behrooz Z. Alizadeh, Terho Lehtimäki, Steve E. Humphries, Naveed Sattar, Bram P. Prins, Peter Rossing, Sophie Visvikis-Siest, Joana A. Revez, Ilja M. Nolte, Stella Trompet, Harold Snieder, Marian Beekman, Diana Marek, Beate St Pourcain, Thorkild I. A. Sørensen, Silvia Naitza, Karen A. Mather, Uwe Völker, Eline Slagboom, Tina Shah, Magdalene C. Jawahar, Jens Baumert, Alexander Teumer, Dorret I. Boomsma, Marcus E. Kleber, Peter Vollenweider, Wolfgang Koenig, Brenda W.J.H. Penninx, Kenneth Rice, Ian J. Deary, Pedro Marques-Vidal, Donna K. Arnett, Eleonora Porcu, Jouke-Jan Hottenga, Maria Sabater-Lleal, Bruce M. Psaty, Matthias Nauck, Dan Mellström, Joel Eriksson, Bernhard T. Baune, Debbie A Lawlor, Catherine Toben, Peter H. Whincup, Toshiko Tanaka, Stavroula Kanoni, Katri Räikkönen, Gonneke Willemsen, Bengt Sennblad, Julian N. Trollor, Yalda Jamshidi, Sarah E. Harris, Jari Lahti, Joshua C. Bis, Peter Durda, Yen Pei C. Chang, Jorgen Engmann, Tom R. Gaunt, Stella Aslibekyan, Anbupalam Thalamuthu, Mary F. Feitosa, Angela Silveira, Tine Jess, Stela McLachlan, J. Wouter Jukema, Chen Lu, Simon P. Mooijaart, Tim D. Spector, Harald Grallert, Winfried März, Alexandros M. Petrelis, Manuel A. R. Ferreira, Meena Kumari, Stochastics, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, APH - Methodology, CHARGE Inflammation Working Group, Epidemiology, Tampere University, Department of Clinical Chemistry, Clinical Medicine, Steno Diabetes Center, University of Copenhagen = Københavns Universitet (KU), University of Groningen [Groningen], Murdoch University, University of Alabama at Birmingham [ Birmingham] (UAB), QIMR Berghofer Medical Research Institute, University College of London [London] (UCL), Helmholtz-Zentrum München (HZM), Leiden University Medical Center (LUMC), University of Bristol [Bristol], University of Washington [Seattle], University of Maryland School of Medicine, University of Maryland System, Vrije Universiteit Amsterdam [Amsterdam] (VU), VU University Medical Center [Amsterdam], University of Heidelberg, Medical Faculty, Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL), Sahlgrenska Academy at University of Gothenburg [Göteborg], National Institute for Health and Welfare [Helsinki], University of Helsinki, William Harvey Research Institute, Barts and the London Medical School, University of Queensland [Brisbane], School of Public Health [Boston], Boston University [Boston] (BU), MRC Institute of Genetics and Molecular Medicine [Edinburgh] (IGMM), University of Edinburgh-Medical Research Council, University of Edinburgh, Amsterdam UMC, Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche [Roma] (CNR), Karolinska Institutet [Stockholm], University of Tampere [Finland], Adelaide Medical School [Australia], University of Adelaide, Universität Greifswald - University of Greifswald, University of New South Wales [Sydney] (UNSW), Prince of Wales Hospital, Ludwig-Maximilians-Universität München (LMU), Baylor College of Medicine (BCM), Baylor University, Boston University School of Medicine (BUSM), VA Boston Healthcare System, Harokopio University of Athens, Max planck Institute for Biology of Ageing [Cologne], Larner College of Medicine [University of Vermont, Burlington], University of Vermont [Burlington], Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-Universität Greifswald, University of Turku, St George's, University of London, Statens Serum Institut [Copenhagen], Medical Faculty [Mannheim], Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Johannes Gutenberg - Universität Mainz (JGU), Vrije Universiteit Medical Centre (VUMC), British Heart Foundation Glasgow Cardiovascular Research Centre (BHF GCRC), University of Glasgow-NHS Greater Glasgow and Clyde, Medical University Graz, Uppsala Universitet [Uppsala], Max Planck Institute for Psycholinguistics, Max-Planck-Gesellschaft, Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], University of Kentucky, Melbourne Medical School [Melbourne], Faculty of Medicine, Dentistry and Health Sciences [Melbourne], University of Melbourne-University of Melbourne, University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), University of Maryland [Baltimore], Queen Mary University of London (QMUL), University of Iceland [Reykjavik], Ludwig Maximilian University [Munich] (LMU), Melbourne School of Population and Global Health [Melbourne], University of Melbourne, Deutsches Herzzentrum München (DHM), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), University of Ulm (UUlm), University of Essex, Greifswald University Hospital, Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), King‘s College London, University of Cambridge [UK] (CAM), Harbor UCLA Medical Center [Torrance, Ca.], Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth), Human Genome Sequencing Center [Houston] (HGSC), Baylor University-Baylor University, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, HUS Children and Adolescents, Lastentautien yksikkö, Children's Hospital, Clinicum, Department of Bacteriology and Immunology, Department of Public Health, Department of Psychology and Logopedics, Research Programs Unit, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Doctoral Programme in Human Behaviour, Life Course Epidemiology (LCE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
Subjects: AcademicSubjects/SCI01140, [SDV]Life Sciences [q-bio], Genome-wide association study, 030204 cardiovascular system & hematology, DISEASE, Pathogenesis, Cohort Studies, 0302 clinical medicine, cytokine, SYSTEMIC-LUPUS-ERYTHEMATOSUS, Association Studies Article, ComputingMilieux_MISCELLANEOUS, Genetics (clinical), Genetics, 0303 health sciences, ARCHITECTURE, CHRONIC INFLAMMATION, 1184 Genetics, developmental biology, physiology, General Medicine, RECEPTOR IL-6R GENE, C-REACTIVE PROTEIN, hla-drb1 gene, 3. Good health, Medical genetics, Medical Genetics, chromosomes, medicine.medical_specialty, SUSCEPTIBILITY LOCI, European Continental Ancestry Group, Locus (genetics), Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, anti-inflammatory agents, White People, 03 medical and health sciences, medicine, Humans, Genetic Predisposition to Disease, Interleukin 6, Molecular Biology, Medicinsk genetik, 030304 developmental biology, PRODUCE IL-6, Interleukin-6, Chromosome, Receptors, Interleukin-6, RHEUMATOID-ARTHRITIS, Interleukin 1 Receptor Antagonist Protein, Gene Expression Regulation, Genetic Loci, CELLS, biology.protein, 1182 Biochemistry, cell and molecular biology, Human genome, 3111 Biomedicine, Genome-Wide Association Study, HLA-DRB1 Chains, Interleukin-1
Abstract: Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10−11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10−10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10−122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
Published: 2021
Full Text: View/download PDF

77. Identifying the Common Genetic Basis of Antidepressant Response

Author: Sara A. Paciga, Richard M. Weinshilboum, Andrew M. McIntosh, Tim B. Bigdeli, Stephanie H. Witt, Sven Cichon, Glyn Lewis, Henning Teismann, Brenda W.J.H. Penninx, Gerome Breen, Roseann E. Peterson, Saira Saeed Mirza, Diego Albani, Lisa Jones, Andreas J. Forstner, Sara Mostafavi, Julien Bryois, Qingqin S. Li, Kenneth S. Kendler, Thomas Damm Als, Fernando S. Goes, Marie Bækvad-Hansen, Nancy L. Pedersen, Gianluigi Forloni, Per Qvist, Carsten Horn, Per Hoffmann, Steven P. Hamilton, Georg Homuth, Michael Gill, Julien Mendlewicz, Katharina Domschke, Volker Arolt, Adrian I. Campos, Christine Søholm Hansen, Scott D. Gordon, Hogni Oskarsson, Peter McGuffin, Oliver Pain, Eric Jorgenson, Victoria S. Marshe, Stacy Steinberg, Bertram Müller-Myhsok, Mark Adams, J. Raymond DePaulo, Rick Jansen, Katherine J. Aitchison, Vassily Trubetskoy, Henry Völzke, Manuel Mattheisen, Bernard Ng, James A. Knowles, Dorret I. Boomsma, Tracy Air, Elisabeth B. Binder, Ian B. Hickie, Christel M. Middeldorp, Tõnu Esko, David M. Hougaard, E.J.C. de Geus, Toni-Kim Clarke, Helena Gaspar, Bernhard T. Baune, Abdel Abdellaoui, Engilbert Sigurdsson, Andres Metspalu, Klaus Berger, Jorge A. Quiroz, Patrick F. Sullivan, Aartjan T.F. Beekman, Thomas Hansen, Panagiotis Ferentinos, Jürgen Wellmann, Miguel E. Rentería, Daniel Umbricht, Marcella Rietschel, Stanley I. Shyn, Chiara Fabbri, Hreinn Stefansson, Jerome C. Foo, Daniel Souery, Zoltán Kutalik, Yu-Li Liu, Paul F. O'Reilly, Michael John Owen, Nese Direk, Douglas F. Levinson, Stuart Montgomery, Hamdi Mbarek, David M. Howard, Guido Bondolfi, Lucía Colodro-Conde, Pippa A. Thomson, Merete Nordentoft, Stefan Kloiber, Yunpeng Wang, Michael Conlon O'Donovan, Grant C.B. Sinnamon, Alexander Viktorin, Hilary K. Finucane, Esben Agerbo, Stefan Herms, Markus M. Nöthen, Till F. M. Andlauer, Divya Mehta, Bradley T. Webb, Joanna M. Biernacka, David J. Porteous, Jordan W. Smoller, Jonathan R. I. Coleman, Dean F. MacKinnon, Farnush Farhadi Hassan Kiadeh, Baptiste Couvy-Duchesne, Evelin Mihailov, Eleanor M. Wigmore, Franziska Degenhardt, Jianxin Shi, Dale R. Nyholt, Enda M. Byrne, Stephan Ripke, Ole Mors, Patrik K. E. Magnusson, Eric J. Lenze, Warren W. Kretzschmar, Masaki Kato, Marcus Ising, Ian Jones, Lynsey S. Hall, Wouter J. Peyrot, Ling Shen, Nader Perroud, Na Cai, Maciej Trzaskowski, Matthias Nauck, Isaac S. Kohane, Enrico Domenici, Fabian Streit, James L. Kennedy, Peter M. Visscher, Valentina Escott-Price, Donald J. MacIntyre, Enrique Castelao, Margarita Rivera, Mojca Z. Dernovsek, John P. Rice, Joseph Zohar, Gail Davies, Andrew C. Heath, Josef Frank, Wesley K. Thompson, Caroline Hayward, Penelope A. Lind, Thorgeir E. Thorgeirsson, Rudolf Uher, Jana Strohmaier, Henriette N. Buttenschøn, Erin C. Dunn, Jonas Bybjerg-Grauholm, Alexander Teumer, Jakob Grove, Eske M. Derks, Nicholas G. Martin, Jodie N. Painter, Myrna M. Weissman, Preben Bo Mortensen, Michel G. Nivard, Catherine Schaefer, Yihan Li, Daniel J. Smith, Shih-Jen Tsai, Niamh Mullins, Jian Yang, Marianne Giørtz Pedersen, Dan Rujescu, Thomas G. Schulze, Lili Milani, Yuri Milaneschi, Giorgio Pistis, James B. Potash, Neven Henigsberg, Nicholas John Craddock, Karen Hodgson, Silviu-Alin Bacanu, Shantel Weinsheimer, Charles F. Reynolds, Johannes H. Smit, Gonneke Willemsen, Futao Zhang, Henning Tiemeier, Grant W. Montgomery, Martin Preisig, Udo Dannlowski, Thalia C. Eley, Thomas Werge, Katherine E. Tansey, Jane H. Christensen, Julia Kraft, Ian J. Deary, Cathryn M. Lewis, Sarah E. Medland, André G. Uitterlinden, Daniel J. Müller, Carsten Bøcker Pedersen, Gustavo Turecki, Hans J. Grabe, Matthew Traylor, Brien P. Riley, Roy H. Perlis, Patrick J. McGrath, Conor V. Dolan, Hualin S. Xi, Jonathan Marchini, Robert A. Schoevers, Albert M. van Hemert, Anders D. Børglum, Susanne Lucae, Jouke-Jan Hottenga, Kari Stefansson, Benoit H. Mulsant, Francis M. Mondimore, Naomi R. Wray, Yang Wu, Wolfgang Maier, Danielle Posthuma, Annamaria Cattaneo, Gregory E. Crawford, Siegfried Kasper, Alessandro Serretti, Tania Carrillo-Roa, Robert Maier, Pamela A. F. Madden, Eva C. Schulte, Jens Treutlein, Joanna Hauser, Sandra Van der Auwera, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Complex Trait Genetics, APH - Methodology, Human genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Reproduction & Development (AR&D), Adult Psychiatry, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Epidemiology, Child and Adolescent Psychiatry / Psychology, and Internal Medicine
Subjects: Oncology, MDD, medicine.medical_specialty, Single-nucleotide polymorphism, Genome-wide association study, Biology, Antidepressant response, Depression, GWAS, Genetics, Polygenic score, SDG 3 - Good Health and Well-being, Internal medicine, Genetic variation, medicine, ddc:610, Genetic association, General Medicine, Heritability, medicine.disease, Schizophrenia, Sample size determination, Settore BIO/14 - Farmacologia, Major depressive disorder
Abstract: Background: Antidepressants are a first-line treatment for depression. However, only a third of individuals experience remission after the first treatment. Common genetic variation, in part, likely regulates antidepressant response, yet the success of previous genome-wide association studies has been limited by sample size. This study performs the largest genetic analysis of prospectively assessed antidepressant response in major depressive disorder to gain insight into the underlying biology and enable out-of-sample prediction.Methods: Genome-wide analysis of remission (nremit = 1852, nnonremit = 3299) and percentage improvement (n = 5218) was performed. Single nucleotide polymorphism–based heritability was estimated using genome-wide complex trait analysis. Genetic covariance with eight mental health phenotypes was estimated using polygenic scores/AVENGEME. Out-of-sample prediction of antidepressant response polygenic scores was assessed. Gene-level association analysis was performed using MAGMA and transcriptome-wide association study. Tissue, pathway, and drug binding enrichment were estimated using MAGMA.Results: Neither genome-wide association study identified genome-wide significant associations. Single nucleotide polymorphism–based heritability was significantly different from zero for remission (h2 = 0.132, SE = 0.056) but not for percentage improvement (h2 = −0.018, SE = 0.032). Better antidepressant response was negatively associated with genetic risk for schizophrenia and positively associated with genetic propensity for educational attainment. Leave-one-out validation of antidepressant response polygenic scores demonstrated significant evidence of out-of-sample prediction, though results varied in external cohorts. Gene-based analyses identified ETV4 and DHX8 as significantly associated with antidepressant response.Conclusions: This study demonstrates that antidepressant response is influenced by common genetic variation, has a genetic overlap schizophrenia and educational attainment, and provides a useful resource for future research. Larger sample sizes are required to attain the potential of genetics for understanding and predicting antidepressant response.
Published: 2022
Full Text: View/download PDF

78. Genetic and Environmental Causes of Individual Differences in Borderline Personality Disorder Features and Loneliness are Partially Shared

Author: Katrina L. Grasby, Ian B. Hickie, Gonneke Willemsen, Lucía Colodro-Conde, Timothy J. Trull, Lannie Ligthart, Julie Aitken Schermer, Nicholas G. Martin, Jane Burns, Dorret I. Boomsma, Biological Psychology, APH - Mental Health, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, and APH - Methodology
Subjects: Adult, Netherlands Twin Register (NTR), multivariate genetic modesl, media_common.quotation_subject, Individuality, 050109 social psychology, Health outcomes, Genetic correlation, 050105 experimental psychology, Correlation, medicine, loneliness, Personality, Humans, 0501 psychology and cognitive sciences, Borderline personality disorder, Genetics (clinical), media_common, Netherlands, 05 social sciences, Australia, Obstetrics and Gynecology, Loneliness, twins, Identity disturbance, Heritability, medicine.disease, genetic correlation, Pediatrics, Perinatology and Child Health, multivariate genetic models, medicine.symptom, Psychology, Clinical psychology
Abstract: Loneliness is related to mental and somatic health outcomes, including borderline personality disorder. Here, we analyze the sources of variation that are responsible for the relationship between borderline personality features (including four dimensions, affective instability, identity disturbance, negative relationships, self-harm and a total score) and loneliness. Using genetically informative data from two large nonclinical samples of adult twin pairs from Australia and the Netherlands (N = 11,329), we estimate the phenotypic, genetic and environmental correlations between self-reported borderline personality features and loneliness. Individual differences in borderline personality and loneliness were best explained by additive genetic factors with heritability estimates h2 = 41% for the borderline personality total score and h2 = 36% for loneliness, with the remaining variation explained by environmental influences that were not shared by twins from the same pair. Genetic and environmental factors influencing borderline personality (total score and four subscales separately) were also partial causes of loneliness. The correlation between loneliness and the borderline personality total score was rph = .51. The genetic correlation was estimated at rg = .64 and the environmental correlation at re = .40. Our study suggests common etiological factors in loneliness and borderline personality features.
Published: 2020
Full Text: View/download PDF

79. Substance use: Interplay between polygenic risk and neighborhood environment

Author: Dorret I. Boomsma, Gonneke Willemsen, Jouke-Jan Hottenga, Karin J. H. Verweij, Joëlle A. Pasman, Jacqueline M. Vink, Iryna O. Fedko, Abdel Abdellaoui, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, APH - Mental Health, APH - Methodology, and Adult Psychiatry
Subjects: Adult, Male, Netherlands Twin Register (NTR), Multifactorial Inheritance, Gene-environment correlation, Substance-Related Disorders, Twins, Poison control, Genome-wide association study, Substance use, Toxicology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Residence Characteristics, Risk Factors, Medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Gene–environment interaction, Socioeconomic status, Netherlands, Pharmacology, biology, business.industry, Neighborhood, Human factors and ergonomics, Middle Aged, biology.organism_classification, Gene-environment interaction, Polygenic scores, Psychiatry and Mental health, Cross-Sectional Studies, Social Class, Cohort, Female, Cannabis, business, Developmental Psychopathology, 030217 neurology & neurosurgery, Demography, Genome-Wide Association Study
Abstract: Contains fulltext : 216912.pdf (Publisher’s version ) (Open Access) Background: Tobacco, alcohol, and cannabis use are prevalent behaviors that pose considerable health risks. Genetic vulnerability and characteristics of the neighborhood of residence form important risk factors for substance use. Possibly, these factors do not act in isolation. This study tested the interaction between neighborhood characteristics and genetic risk (gene-environment interaction, GxE) and the association between these classes of risk factors (gene-environment correlation, rGE) in substance use. Methods: Two polygenic scores (PGS) each (based on different discovery datasets) were created for smoking initiation, cigarettes per day, and glasses of alcohol per week based on summary statistics of different genome-wide association studies (GWAS). For cannabis initiation one PGS was created. These PGS were used to predict their respective phenotype in a large population-based sample from the Netherlands Twin Register (N = 6,567). Neighborhood characteristics as retrieved from governmental registration systems were factor analyzed and resulting measures of socioeconomic status (SES) and metropolitanism were used as predictors. Results: There were (small) main effects of neighborhood characteristics and PGS on substance use. One of the 14 tested GxE effects was significant, such that the PGS was more strongly associated with alcohol use in individuals with high SES. This was effect was only significant for one out of two PGS. There were weak indications of rGE, mainly with age and cohort covariates. Conclusion: We conclude that both genetic and neighborhood-level factors are predictors for substance use. More research is needed to establish the robustness of the findings on the interplay between these factors. 8 p.
Published: 2020
Full Text: View/download PDF

80. Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders

Author: Gabriëlla A.M. Blokland, Jakob Grove, Chia-Yen Chen, Chris Cotsapas, Stuart Tobet, Robert Handa, David St Clair, Todd Lencz, Bryan J. Mowry, Sathish Periyasamy, Murray J. Cairns, Paul A. Tooney, Jing Qin Wu, Brian Kelly, George Kirov, Patrick F. Sullivan, Aiden Corvin, Brien P. Riley, Tõnu Esko, Lili Milani, Erik G. Jönsson, Aarno Palotie, Hannelore Ehrenreich, Martin Begemann, Agnes Steixner-Kumar, Pak C. Sham, Nakao Iwata, Daniel R. Weinberger, Pablo V. Gejman, Alan R. Sanders, Joseph D. Buxbaum, Dan Rujescu, Ina Giegling, Bettina Konte, Annette M. Hartmann, Elvira Bramon, Robin M. Murray, Michele T. Pato, Jimmy Lee, Ingrid Melle, Espen Molden, Roel A. Ophoff, Andrew McQuillin, Nicholas J. Bass, Rolf Adolfsson, Anil K. Malhotra, Nicholas G. Martin, Janice M. Fullerton, Philip B. Mitchell, Peter R. Schofield, Andreas J. Forstner, Franziska Degenhardt, Sabrina Schaupp, Ashley L. Comes, Manolis Kogevinas, José Guzman-Parra, Andreas Reif, Fabian Streit, Lea Sirignano, Sven Cichon, Maria Grigoroiu-Serbanescu, Joanna Hauser, Jolanta Lissowska, Fermin Mayoral, Bertram Müller-Myhsok, Beata Świątkowska, Thomas G. Schulze, Markus M. Nöthen, Marcella Rietschel, John Kelsoe, Marion Leboyer, Stéphane Jamain, Bruno Etain, Frank Bellivier, John B. Vincent, Martin Alda, Claire O’Donovan, Pablo Cervantes, Joanna M. Biernacka, Mark Frye, Susan L. McElroy, Laura J. Scott, Eli A. Stahl, Mikael Landén, Marian L. Hamshere, Olav B. Smeland, Srdjan Djurovic, Arne E. Vaaler, Ole A. Andreassen, Bernhard T. Baune, Tracy Air, Martin Preisig, Rudolf Uher, Douglas F. Levinson, Myrna M. Weissman, James B. Potash, Jianxin Shi, James A. Knowles, Roy H. Perlis, Susanne Lucae, Dorret I. Boomsma, Brenda W.J.H. Penninx, Jouke-Jan Hottenga, Eco J.C. de Geus, Gonneke Willemsen, Yuri Milaneschi, Henning Tiemeier, Hans J. Grabe, Alexander Teumer, Sandra Van der Auwera, Uwe Völker, Steven P. Hamilton, Patrik K.E. Magnusson, Alexander Viktorin, Divya Mehta, Niamh Mullins, Mark J. Adams, Gerome Breen, Andrew M. McIntosh, Cathryn M. Lewis, David M. Hougaard, Merete Nordentoft, Ole Mors, Preben B. Mortensen, Thomas Werge, Thomas D. Als, Anders D. Børglum, Tracey L. Petryshen, Jordan W. Smoller, Jill M. Goldstein, Stephan Ripke, Benjamin M. Neale, James T.R. Walters, Kai-How Farh, Peter A. Holmans, Phil Lee, Brendan Bulik-Sullivan, David A. Collier, Hailiang Huang, Tune H. Pers, Ingrid Agartz, Esben Agerbo, Margot Albus, Madeline Alexander, Farooq Amin, Silviu A. Bacanu, Richard A. Belliveau, Judit Bene, Sarah E. Bergen, Elizabeth Bevilacqua, Tim B. Bigdeli, Donald W. Black, Richard Bruggeman, Nancy G. Buccola, Randy L. Buckner, William Byerley, Wiepke Cahn, Guiqing Cai, Dominique Campion, Rita M. Cantor, Vaughan J. Carr, Noa Carrera, Stanley V. Catts, Kimberly D. Chambert, Raymond C.K. Chan, Ronald Y.L. Chen, Eric Y.H. Chen, Wei Cheng, Eric F.C. Cheung, Siow Ann Chong, C. Robert Cloninger, David Cohen, Nadine Cohen, Paul Cormican, Nick Craddock, James J. Crowley, David Curtis, Michael Davidson, Kenneth L. Davis, Jurgen Del Favero, Ditte Demontis, Dimitris Dikeos, Timothy Dinan, Gary Donohoe, Elodie Drapeau, Jubao Duan, Frank Dudbridge, Naser Durmishi, Peter Eichhammer, Johan Eriksson, Valentina Escott-Price, Laurent Essioux, Ayman H. Fanous, Martilias S. Farrell, Josef Frank, Lude Franke, Robert Freedman, Nelson B. Freimer, Marion Friedl, Joseph I. Friedman, Menachem Fromer, Giulio Genovese, Lyudmila Georgieva, Paola Giusti-Rodríguez, Stephanie Godard, Jacqueline I. Goldstein, Vera Golimbet, Srihari Gopal, Jacob Gratten, Lieuwe de Haan, Christian Hammer, Mark Hansen, Thomas Hansen, Vahram Haroutunian, Frans A. Henskens, Stefan Herms, Joel N. Hirschhorn, Per Hoffmann, Andrea Hofman, Mads V. Hollegaard, Masashi Ikeda, Inge Joa, Antonio Julià, René S. Kahn, Luba Kalaydjieva, Sena Karachanak-Yankova, Juha Karjalainen, David Kavanagh, Matthew C. Keller, James L. Kennedy, Andrey Khrunin, Yunjung Kim, Janis Klovins, Vaidutis Kucinskas, Zita Ausrele Kucinskiene, Hana Kuzelova-Ptackova, Anna K. Kähler, Claudine Laurent, Jimmy Lee Chee Keong, S. Hong Lee, Sophie E. Legge, Bernard Lerer, Miaoxin Li, Tao Li, Kung-Yee Liang, Jeffrey Lieberman, Svetlana Limborska, Carmel M. Loughland, Jan Lubinski, Jouko Lönnqvist, Milan Macek, Brion S. Maher, Wolfgang Maier, Jacques Mallet, Sara Marsal, Manuel Mattheisen, Morten Mattingsdal, Robert W. McCarley, Colm McDonald, Sandra Meier, Carin J. Meijer, Bela Melegh, Raquelle I. Mesholam-Gately, Andres Metspalu, Patricia T. Michie, Vihra Milanova, Younes Mokrab, Derek W. Morris, Kieran C. Murphy, Inez Myin-Germeys, Mari Nelis, Igor Nenadic, Deborah A. Nertney, Gerald Nestadt, Kristin K. Nicodemus, Liene Nikitina-Zake, Laura Nisenbaum, Annelie Nordin, Eadbhard O’Callaghan, Colm O’Dushlaine, F. Anthony O’Neill, Sang-Yun Oh, Ann Olincy, Line Olsen, Jim Van Os, Christos Pantelis, George N. Papadimitriou, Sergi Papiol, Elena Parkhomenko, Tiina Paunio, Milica Pejovic-Milovancevic, Diana O. Perkins, Olli Pietiläinen, Jonathan Pimm, Andrew J. Pocklington, John Powell, Alkes Price, Ann E. Pulver, Shaun M. Purcell, Digby Quested, Henrik B. Rasmussen, Abraham Reichenberg, Mark A. Reimers, Alexander L. Richards, Joshua L. Roffman, Panos Roussos, Douglas M. Ruderfer, Veikko Salomaa, Ulrich Schall, Christian R. Schubert, Sibylle G. Schwab, Edward M. Scolnick, Rodney J. Scott, Larry J. Seidman, Engilbert Sigurdsson, Teimuraz Silagadze, Jeremy M. Silverman, Kang Sim, Petr Slominsky, Hon-Cheong So, Chris C.A. Spencer, Hreinn Stefansson, Stacy Steinberg, Elisabeth Stogmann, Richard E. Straub, Eric Strengman, Jana Strohmaier, T. Scott Stroup, Mythily Subramaniam, Jaana Suvisaari, Dragan M. Svrakic, Jin P. Szatkiewicz, Erik Söderman, Srinivas Thirumalai, Draga Toncheva, Sarah Tosato, Juha Veijola, John Waddington, Dermot Walsh, Dai Wang, Qiang Wang, Bradley T. Webb, Mark Weiser, Dieter B. Wildenauer, Nigel M. Williams, Stephanie Williams, Stephanie H. Witt, Aaron R. Wolen, Emily H.M. Wong, Brandon K. Wormley, Hualin Simon Xi, Clement C. Zai, Xuebin Zheng, Fritz Zimprich, Naomi R. Wray, Kari Stefansson, Peter M. Visscher, Douglas H.R. Blackwood, Ariel Darvasi, Enrico Domenici, Michael Gill, Hugh Gurling, Christina M. Hultman, Assen V. Jablensky, Kenneth S. Kendler, Jo Knight, Qingqin S. Li, Jianjun Liu, Steven A. McCarroll, Jennifer L. Moran, Michael J. Owen, Carlos N. Pato, Danielle Posthuma, Pamela Sklar, Jens R. Wendland, Mark J. Daly, Michael C. O’Donovan, Peter Donnelly, Ines Barroso, Jenefer M. Blackwell, Matthew A. Brown, Juan P. Casas, Panos Deloukas, Audrey Duncanson, Janusz Jankowski, Hugh S. Markus, Christopher G. Mathew, Colin N.A. Palmer, Robert Plomin, Anna Rautanen, Stephen J. Sawcer, Richard C. Trembath, Ananth C. Viswanathan, Nicholas W. Wood, Gavin Band, Céline Bellenguez, Colin Freeman, Eleni Giannoulatou, Garrett Hellenthal, Richard Pearson, Matti Pirinen, Amy Strange, Zhan Su, Damjan Vukcevic, Cordelia Langford, Hannah Blackburn, Suzannah J. Bumpstead, Serge Dronov, Sarah Edkins, Matthew Gillman, Emma Gray, Rhian Gwilliam, Naomi Hammond, Sarah E. Hunt, Alagurevathi Jayakumar, Jennifer Liddle, Owen T. McCann, Simon C. Potter, Radhi Ravindrarajah, Michelle Ricketts, Avazeh Tashakkori-Ghanbaria, Matthew Waller, Paul Weston, Pamela Whittaker, Sara Widaa, Mark I. McCarthy, Maria J. Arranz, Steven Bakker, Stephan Bender, Benedicto Crespo-Facorro, Jeremy Hall, Conrad Iyegbe, Stephen Lawrie, Kuang Lin, Don H. Linszen, Ignacio Mata, Muriel Walshe, Matthias Weisbrod, Durk Wiersma, Vassily Trubetskoy, Yunpeng Wang, Jonathan R.I. Coleman, Héléna A. Gaspar, Christiaan A. de Leeuw, Jennifer M. Whitehead Pavlides, Maciej Trzaskowski, Enda M. Byrne, Liam Abbott, Huda Akil, Diego Albani, Ney Alliey-Rodriguez, Adebayo Anjorin, Verneri Antilla, Swapnil Awasthi, Judith A. Badner, Marie Bækvad-Hansen, Jack D. Barchas, Nicholas Bass, Michael Bauer, Richard Belliveau, Carsten Bøcker Pedersen, Erlend Bøen, Marco P. Boks, James Boocock, Monika Budde, William Bunney, Margit Burmeister, Jonas Bybjerg-Grauholm, Miquel Casas, Felecia Cerrato, Kimberly Chambert, Alexander W. Charney, Danfeng Chen, Claire Churchhouse, Toni-Kim Clarke, William Coryell, David W. Craig, Cristiana Cruceanu, Piotr M. Czerski, Anders M. Dale, Simone de Jong, Jurgen Del-Favero, J. Raymond DePaulo, Amanda L. Dobbyn, Ashley Dumont, Torbjørn Elvsåshagen, Chun Chieh Fan, Sascha B. Fischer, Matthew Flickinger, Tatiana M. Foroud, Liz Forty, Christine Fraser, Katrin Gade, Diane Gage, Julie Garnham, Claudia Giambartolomei, Marianne Giørtz Pedersen, Jaqueline Goldstein, Scott D. Gordon, Katherine Gordon-Smith, Elaine K. Green, Melissa J. Green, Tiffany A. Greenwood, Weihua Guan, Martin Hautzinger, Urs Heilbronner, Maria Hipolito, Dominic Holland, Laura Huckins, Jessica S. Johnson, Radhika Kandaswamy, Robert Karlsson, Sarah Kittel-Schneider, Anna C. Koller, Ralph Kupka, Catharina Lavebratt, Jacob Lawrence, William B. Lawson, Markus Leber, Phil H. Lee, Shawn E. Levy, Jun Z. Li, Chunyu Liu, Anna Maaser, Donald J. MacIntyre, Pamela B. Mahon, Lina Martinsson, Steve McCarroll, Peter McGuffin, Melvin G. McInnis, James D. McKay, Helena Medeiros, Sarah E. Medland, Fan Meng, Grant W. Montgomery, Thomas W. Mühleisen, Hoang Nguyen, Caroline M. Nievergelt, Annelie Nordin Adolfsson, Evaristus A. Nwulia, Claire O'Donovan, Loes M. Olde Loohuis, Anil P.S. Ori, Lilijana Oruc, Urban Ösby, Amy Perry, Andrea Pfennig, Eline J. Regeer, Céline S. Reinbold, John P. Rice, Fabio Rivas, Margarita Rivera, Euijung Ryu, Cristina Sánchez-Mora, Alan F. Schatzberg, William A. Scheftner, Nicholas J. Schork, Cynthia Shannon Weickert, Tatyana Shehktman, Paul D. Shilling, Claire Slaney, Janet L. Sobell, Christine Søholm Hansen, Anne T. Spijker, Michael Steffens, John S. Strauss, Szabolcs Szelinger, Robert C. Thompson, Thorgeir E. Thorgeirsson, Jens Treutlein, Helmut Vedder, Weiqing Wang, Stanley J. Watson, Thomas W. Weickert, Simon Xi, Wei Xu, Allan H. Young, Peter Zandi, Peng Zhang, Sebastian Zöllner, Abdel Abdellaoui, Tracy M. Air, Till F.M. Andlauer, Silviu-Alin Bacanu, Aartjan T.F. Beekman, Elisabeth B. Binder, Julien Bryois, Henriette N. Buttenschøn, Na Cai, Enrique Castelao, Jane Hvarregaard Christensen, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Gregory E. Crawford, Gail Davies, Ian J. Deary, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Jerome C. Foo, Fernando S. Goes, Lynsey S. Hall, Thomas F. Hansen, Ian B. Hickie, Georg Homuth, Carsten Horn, David M. Howard, Marcus Ising, Rick Jansen, Ian Jones, Lisa A. Jones, Eric Jorgenson, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Dean F. MacKinnon, Robert M. Maier, Jonathan Marchini, Hamdi Mbarek, Patrick McGrath, Christel M. Middeldorp, Evelin Mihailov, Francis M. Mondimore, Sara Mostafavi, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. Nyholt, Paul F. O'Reilly, Hogni Oskarsson, Jodie N. Painter, Roseann E. Peterson, Wouter J. Peyrot, Giorgio Pistis, Jorge A. Quiroz, Per Qvist, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Stanley I. Shyn, Grant C.B. Sinnamon, Johannes H. Smit, Daniel J. Smith, Katherine E. Tansey, Henning Teismann, Wesley Thompson, Pippa A. Thomson, Matthew Traylor, André G. Uitterlinden, Daniel Umbricht, Albert M. van Hemert, Shantel Marie Weinsheimer, Jürgen Wellmann, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Volker Arolt, Klaus Berger, Udo Dannlowski, Katharina Domschke, Caroline Hayward, Andrew C. Heath, Stefan Kloiber, Glyn Lewis, Pamela AF. Madden, Patrik K. Magnusson, Preben Bo Mortensen, Michael C. O'Donovan, Sara A. Paciga, Nancy L. Pedersen, David J. Porteous, Catherine Schaefer, Henry Völzke, Marco Bortolato, Janita Bralten, Cynthia M. Bulik, Christie L. Burton, Caitlin E. Carey, Lea K. Davis, Laramie E. Duncan, Howard J. Edenberg, Lauren Erdman, Stephen V. Faraone, Slavina B. Goleva, Wei Guo, Christopher Hübel, Laura M. Huckins, Ekaterina A. Khramtsova, Joanna Martin, Carol A. Mathews, Elise Robinson, Eli Stahl, Barbara E. Stranger, Michela Traglia, Raymond K. Walters, Lauren A. Weiss, Stacey J. Winham, Yin Yao, Kristjar Skajaa, Markus Nöthen, Michael Owen, Robert H. Yolken, Niels Plath, Jonathan Mill, Daniel Geschwind, Psychiatry 1, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, Centre of Excellence in Complex Disease Genetics, Research Programme of Molecular Medicine, Research Programs Unit, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, Functional Genomics, Biological Psychology, APH - Mental Health, APH - Methodology, Sociology and Social Gerontology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Blokland, Gabriella AM, Grove, Jakob, Chen, Chia Yen, Cotsapas, Chris, Tobet, Stuart, Handa, Robert, Lee, Sang Hong, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Sex Differences Cross-Disorder Analysis Group of the Psychiatric Genomics Consortium, iPSYCH, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Human genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Reproduction & Development (AR&D), Child and Adolescent Psychiatry / Psychology, Adult Psychiatry, ANS - Complex Trait Genetics, and ANS - Mood, Anxiety, Psychosis, Stress & Sleep
Subjects: 0301 basic medicine, Male, Bipolar Disorder, Schizophrenia/genetics, LD SCORE REGRESSION, Genome-wide association study, 0302 clinical medicine, Receptors, SCHIZOPHRENIA, Psychotic Disorders/genetics, KYNURENINE PATHWAY METABOLISM, Genetics, RISK, Sex Characteristics, Vascular Endothelial Growth Factor, Bipolar Disorder/genetics, Major/genetics, Single Nucleotide, AFFECTIVE STIMULI IMPACT, Schizophrenia, Sulfurtransferases, Major depressive disorder, Female, Depressive Disorder, Major/genetics, Bipolar disorder, Locus (genetics), Genomics, Biology, Polymorphism, Single Nucleotide, Article, DYSPHORIC MOOD, 03 medical and health sciences, Sex differences, medicine, Humans, Genetic Predisposition to Disease, ddc:610, Polymorphism, GENOME-WIDE ASSOCIATION, Genotype-by-sex interaction, Biological Psychiatry, Depressive Disorder, Major, Depressive Disorder, GENDER-DIFFERENCES, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], PARAVENTRICULAR NUCLEUS, 3112 Neurosciences, Endothelial Cells, MAJOR DEPRESSION, medicine.disease, Genetic architecture, 030104 developmental biology, Mood, Receptors, Vascular Endothelial Growth Factor, Psychotic Disorders, 3111 Biomedicine, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Contains fulltext : 248656.pdf (Publisher’s version ) (Closed access) BACKGROUND: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. METHODS: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. RESULTS: Across disorders, genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10(-8)), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10(-6)) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10(-7); rs73033497, p = 8.8 × 10(-7); rs7914279, p = 6.4 × 10(-7)), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10(-7)) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10(-7)), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10(-7)) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). CONCLUSIONS: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels.
Published: 2022
Full Text: View/download PDF

81. Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders

Author: Andreas J. Forstner, Martin Alda, Manolis Kogevinas, Pak C. Sham, Patrick F. Sullivan, Michele T. Pato, John R. Kelsoe, Paul A. Tooney, Steven P. Hamilton, Dorret I. Boomsma, Gerome Breen, Tracy Air, Hannelore Ehrenreich, Nakao Iwata, Jill M. Goldstein, Olav B. Smeland, Daniel R. Weinberger, Andrew McQuillin, Stuart A. Tobet, Elvira Bramon, Gabriëlla A.M. Blokland, Jing Qin Wu, Erik G. Jönsson, Peter R. Schofield, Fabian Streit, Nicholas Bass, Aarno Palotie, Brian Kelly, Cathryn M. Lewis, Srdjan Djurovic, Thomas Damm Als, Chia-Yen Chen, Bettina Konte, Joanna Hauser, Claire O'Donovan, Laura J. Scott, Hans J. Grabe, Murray J. Cairns, Rudolf Uher, Pablo Cervantes, Nicholas G. Martin, James A. Knowles, Aiden Corvin, Espen Molden, Lili Milani, Andreas Reif, Maria Grigoroiu-Serbanescu, George Kirov, Yuri Milaneschi, David St Clair, Eco J. C. de Geus, Robert Handa, Tõnu Esko, Alexander Teumer, Anders D. Børglum, Divya Mehta, Roel A. Ophoff, Susanne Lucae, Henning Tiemeier, Marion Leboyer, Ina Giegling, Alan R. Sanders, Jouke-Jan Hottenga, Pablo V. Gejman, Bernhard T. Baune, Brenda W.J.H. Penninx, Chris Cotsapas, Martin Preisig, Thomas Werge, Jakob Grove, Ingrid Melle, Jordan W. Smoller, Marcella Rietschel, Myrna M. Weissman, Preben Bo Mortensen, Philip B. Mitchell, Jolanta Lissowska, Andrew M. McIntosh, Annette M. Hartmann, Ole A. Andreassen, Lea Sirignano, John B. Vincent, Niamh Mullins, Jimmy Lee, Gonneke Willemsen, Marian L. Hamshere, Rolf Adolfsson, Mark A. Frye, Markus M. Nöthen, Jianxin Shi, Ashley L. Comes, Robin M. Murray, Patrik K. E. Magnusson, Frank Bellivier, Stéphane Jamain, Ole Mors, Sven Cichon, Uwe Völker, Fermín Mayoral, Bryan J. Mowry, Bruno Etain, James B. Potash, Beata Świątkowska, Bertram Müller-Myhsok, Mikael Landén, Tracey L. Petryshen, Franziska Degenhardt, Mark Adams, Dan Rujescu, Jose Guzman-Parra, Thomas G. Schulze, Merete Nordentoft, Joseph D. Buxbaum, Janice M. Fullerton, Brien P. Riley, Roy H. Perlis, Arne E. Vaaler, David M. Hougaard, Eli A. Stahl, Susan L. McElroy, Sabrina K. Schaupp, Martin Begemann, Sandra Van der Auwera, Todd Lencz, Joanna M. Biernacka, Agnes A. Steixner-Kumar, Douglas F. Levinson, Sathish Periyasamy, Alexander Viktorin, and Anil K. Malhotra
Subjects: Genetics, 0303 health sciences, Medizin, Locus (genetics), Genomics, Biology, medicine.disease, Genetic architecture, 03 medical and health sciences, 0302 clinical medicine, Mood, medicine, Major depressive disorder, Bipolar disorder, Gene, NKAIN2 Gene, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: BACKGROUNDSex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk.METHODSWe conducted the largest to date genome-wide genotype–by–sex (GxS) interaction of risk for these disorders, using 85,735 cases (33,403 SCZ, 19,924 BIP, 32,408 MDD) and 109,946 controls from the Psychiatric Genomics Consortium (PGC) and iPSYCH.RESULTSAcross disorders, genome-wide significant SNP-by-sex interaction was detected for a locus encompassingNKAIN2(rs117780815;p=3.2×10−8), that interacts with sodium/potassium-transporting ATPase enzymes implicating neuronal excitability. Three additional loci showed evidence (p−6) for cross-disorder GxS interaction (rs7302529,p=1.6×10−7; rs73033497,p=8.8×10−7; rs7914279,p=6.4×10−7) implicating various functions. Gene-based analyses identified GxS interaction across disorders (p=8.97×10−7) with transcriptional inhibitorSLTM. Most significant in SCZ was aMOCOSgene locus (rs11665282;p=1.5×10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509;p=1.1×10−7) in a locus containingIDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant GxS of genes regulating vascular endothelial growth factor (VEGF) receptor signaling in MDD (pFDRCONCLUSIONSIn the largest genome-wide GxS analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development, immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway enrichment levels.
Published: 2022

82. Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Author: Niamh Mullins, JooEun Kang, Adrian I. Campos, Jonathan R.I. Coleman, Alexis C. Edwards, Hanga Galfalvy, Daniel F. Levey, Adriana Lori, Andrey Shabalin, Anna Starnawska, Mei-Hsin Su, Hunna J. Watson, Mark Adams, Swapnil Awasthi, Michael Gandal, Jonathan D. Hafferty, Akitoyo Hishimoto, Minsoo Kim, Satoshi Okazaki, Ikuo Otsuka, Stephan Ripke, Erin B. Ware, Andrew W. Bergen, Wade H. Berrettini, Martin Bohus, Harry Brandt, Xiao Chang, Wei J. Chen, Hsi-Chung Chen, Steven Crawford, Scott Crow, Emily DiBlasi, Philibert Duriez, Fernando Fernández-Aranda, Manfred M. Fichter, Steven Gallinger, Stephen J. Glatt, Philip Gorwood, Yiran Guo, Hakon Hakonarson, Katherine A. Halmi, Hai-Gwo Hwu, Sonia Jain, Stéphane Jamain, Susana Jiménez-Murcia, Craig Johnson, Allan S. Kaplan, Walter H. Kaye, Pamela K. Keel, James L. Kennedy, Kelly L. Klump, Dong Li, Shih-Cheng Liao, Klaus Lieb, Lisa Lilenfeld, Chih-Min Liu, Pierre J. Magistretti, Christian R. Marshall, James E. Mitchell, Eric T. Monson, Richard M. Myers, Dalila Pinto, Abigail Powers, Nicolas Ramoz, Stefan Roepke, Vsevolod Rozanov, Stephen W. Scherer, Christian Schmahl, Marcus Sokolowski, Michael Strober, Laura M. Thornton, Janet Treasure, Ming T. Tsuang, Stephanie H. Witt, D. Blake Woodside, Zeynep Yilmaz, Lea Zillich, Rolf Adolfsson, Ingrid Agartz, Tracy M. Air, Martin Alda, Lars Alfredsson, Ole A. Andreassen, Adebayo Anjorin, Vivek Appadurai, María Soler Artigas, Sandra Van der Auwera, M. Helena Azevedo, Nicholas Bass, Claiton H.D. Bau, Bernhard T. Baune, Frank Bellivier, Klaus Berger, Joanna M. Biernacka, Tim B. Bigdeli, Elisabeth B. Binder, Michael Boehnke, Marco P. Boks, Rosa Bosch, David L. Braff, Richard Bryant, Monika Budde, Enda M. Byrne, Wiepke Cahn, Miguel Casas, Enrique Castelao, Jorge A. Cervilla, Boris Chaumette, Sven Cichon, Aiden Corvin, Nicholas Craddock, David Craig, Franziska Degenhardt, Srdjan Djurovic, Howard J. Edenberg, Ayman H. Fanous, Jerome C. Foo, Andreas J. Forstner, Mark Frye, Janice M. Fullerton, Justine M. Gatt, Pablo V. Gejman, Ina Giegling, Hans J. Grabe, Melissa J. Green, Eugenio H. Grevet, Maria Grigoroiu-Serbanescu, Blanca Gutierrez, Jose Guzman-Parra, Steven P. Hamilton, Marian L. Hamshere, Annette Hartmann, Joanna Hauser, Stefanie Heilmann-Heimbach, Per Hoffmann, Marcus Ising, Ian Jones, Lisa A. Jones, Lina Jonsson, René S. Kahn, John R. Kelsoe, Kenneth S. Kendler, Stefan Kloiber, Karestan C. Koenen, Manolis Kogevinas, Bettina Konte, Marie-Odile Krebs, Mikael Landén, Jacob Lawrence, Marion Leboyer, Phil H. Lee, Douglas F. Levinson, Calwing Liao, Jolanta Lissowska, Susanne Lucae, Fermin Mayoral, Susan L. McElroy, Patrick McGrath, Peter McGuffin, Andrew McQuillin, Sarah E. Medland, Divya Mehta, Ingrid Melle, Yuri Milaneschi, Philip B. Mitchell, Esther Molina, Gunnar Morken, Preben Bo Mortensen, Bertram Müller-Myhsok, Caroline Nievergelt, Vishwajit Nimgaonkar, Markus M. Nöthen, Michael C. O’Donovan, Roel A. Ophoff, Michael J. Owen, Carlos Pato, Michele T. Pato, Brenda W.J.H. Penninx, Jonathan Pimm, Giorgio Pistis, James B. Potash, Robert A. Power, Martin Preisig, Digby Quested, Josep Antoni Ramos-Quiroga, Andreas Reif, Marta Ribasés, Vanesa Richarte, Marcella Rietschel, Margarita Rivera, Andrea Roberts, Gloria Roberts, Guy A. Rouleau, Diego L. Rovaris, Dan Rujescu, Cristina Sánchez-Mora, Alan R. Sanders, Peter R. Schofield, Thomas G. Schulze, Laura J. Scott, Alessandro Serretti, Jianxin Shi, Stanley I. Shyn, Lea Sirignano, Pamela Sklar, Olav B. Smeland, Jordan W. Smoller, Edmund J.S. Sonuga-Barke, Gianfranco Spalletta, John S. Strauss, Beata Świątkowska, Maciej Trzaskowski, Gustavo Turecki, Laura Vilar-Ribó, John B. Vincent, Henry Völzke, James T.R. Walters, Cynthia Shannon Weickert, Thomas W. Weickert, Myrna M. Weissman, Leanne M. Williams, Naomi R. Wray, Clement C. Zai, Allison E. Ashley-Koch, Jean C. Beckham, Elizabeth R. Hauser, Michael A. Hauser, Nathan A. Kimbrel, Jennifer H. Lindquist, Benjamin McMahon, David W. Oslin, Xuejun Qin, Esben Agerbo, Anders D. Børglum, Gerome Breen, Annette Erlangsen, Tõnu Esko, Joel Gelernter, David M. Hougaard, Ronald C. Kessler, Henry R. Kranzler, Qingqin S. Li, Nicholas G. Martin, Andrew M. McIntosh, Ole Mors, Merete Nordentoft, Catherine M. Olsen, David Porteous, Robert J. Ursano, Danuta Wasserman, Thomas Werge, David C. Whiteman, Cynthia M. Bulik, Hilary Coon, Ditte Demontis, Anna R. Docherty, Po-Hsiu Kuo, Cathryn M. Lewis, J. John Mann, Miguel E. Rentería, Daniel J. Smith, Eli A. Stahl, Murray B. Stein, Fabian Streit, Virginia Willour, Douglas M. Ruderfer, Manuel Mattheisen, Abdel Abdellaoui, Mark J. Adams, Till F.M. Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T.F. Beekman, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Jane Hvarregaard Christensen, Toni-Kim Clarke, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E. Crawford, Gail Davies, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Josef Frank, Héléna A. Gaspar, Michael Gill, Fernando S. Goes, Scott D. Gordon, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Volker Arolt, Dorret I. Boomsma, Udo Dannlowski, E.J.C. de Geus, J. Raymond Depaulo, Enrico Domenici, Katharina Domschke, Jakob Grove, Lynsey S. Hall, Christine Søholm Hansen, Thomas F. Hansen, Stefan Herms, Ian B. Hickie, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Howard, Rick Jansen, Eric Jorgenson, James A. Knowles, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Donald J. MacIntyre, Dean F. MacKinnon, Robert M. Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Christel M. Middeldorp, Evelin Mihailov, Lili Milani, Francis M. Mondimore, Grant W. Montgomery, Sara Mostafavi, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. Nyholt, Paul F. O’Reilly, Hogni Oskarsson, Caroline Hayward, Andrew C. Heath, Glyn Lewis, Pamela A.F. Madden, Patrik K. Magnusson, Andres Metspalu, Sara A. Paciga, Nancy L. Pedersen, Jodie N. Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E. Peterson, Wouter J. Peyrot, Danielle Posthuma, Jorge A. Quiroz, Per Qvist, John P. Rice, Brien P. Riley, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Engilbert Sigurdsson, Grant C.B. Sinnamon, Johannes H. Smit, Hreinn Stefansson, Stacy Steinberg, Jana Strohmaier, Katherine E. Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A. Thomson, Thorgeir E. Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G. Uitterlinden, Daniel Umbricht, Albert M. van Hemert, Alexander Viktorin, Peter M. Visscher, Yunpeng Wang, Bradley T. Webb, Roy H. Perlis, David J. Porteous, Catherine Schaefer, Kari Stefansson, Henning Tiemeier, Rudolf Uher, Patrick F. Sullivan, Kevin S. O’Connell, Brandon Coombes, Zhen Qiao, Thomas D. Als, Sigrid Børte, Alexander W. Charney, Ole Kristian Drange, Michael J. Gandal, Saskia P. Hagenaars, Masashi Ikeda, Nolan Kamitaki, Kristi Krebs, Georgia Panagiotaropoulou, Brian M. Schilder, Laura G. Sloofman, Bendik S. Winsvold, Hong-Hee Won, Liliya Abramova, Kristina Adorjan, Mariam Al Eissa, Diego Albani, Ney Alliey-Rodriguez, Verneri Antilla, Anastasia Antoniou, Ji Hyun Baek, Michael Bauer, Eva C. Beins, Sarah E. Bergen, Armin Birner, Erlend Bøen, Murielle Brum, Ben M. Brumpton, Nathalie Brunkhorst-Kanaan, William Byerley, Murray Cairns, Miquel Casas, Pablo Cervantes, Cristiana Cruceanu, Alfredo Cuellar-Barboza, Julie Cunningham, David Curtis, Piotr M. Czerski, Anders M. Dale, Nina Dalkner, Friederike S. David, Amanda L. Dobbyn, Athanassios Douzenis, Torbjørn Elvsåshagen, I. Nicol Ferrier, Alessia Fiorentino, Tatiana M. Foroud, Liz Forty, Oleksandr Frei, Nelson B. Freimer, Louise Frisén, Katrin Gade, Julie Garnham, Ian R. Gizer, Katherine Gordon-Smith, Tiffany A. Greenwood, José Guzman-Parra, Kyooseob Ha, Magnus Haraldsson, Martin Hautzinger, Urs Heilbronner, Dennis Hellgren, Peter A. Holmans, Laura Huckins, Jessica S. Johnson, Janos L. Kalman, Yoichiro Kamatani, Sarah Kittel-Schneider, Maria Koromina, Thorsten M. Kranz, Michiaki Kubo, Ralph Kupka, Steven A. Kushner, Catharina Lavebratt, Markus Leber, Heon-Jeong Lee, Shawn E. Levy, Catrin Lewis, Martin Lundberg, Sigurdur H. Magnusson, Adam Maihofer, Dolores Malaspina, Eirini Maratou, Lina Martinsson, Nathaniel W. McGregor, James D. McKay, Helena Medeiros, Vincent Millischer, Jennifer L. Moran, Derek W. Morris, Thomas W. Mühleisen, Niamh O’Brien, Claire O’Donovan, Loes M. Olde Loohuis, Lilijana Oruc, Sergi Papiol, Antonio F. Pardiñas, Amy Perry, Andrea Pfennig, Evgenia Porichi, Towfique Raj, Mark H. Rapaport, J. Raymond DePaulo, Eline J. Regeer, Fabio Rivas, Julian Roth, Panos Roussos, Fanny Senner, Sally Sharp, Paul D. Shilling, Claire Slaney, Janet L. Sobell, Maria Soler Artigas, Anne T. Spijker, Dan J. Stein, Chikashi Terao, Claudio Toma, Paul Tooney, Evangelia-Eirini Tsermpini, Marquis P. Vawter, Helmut Vedder, Simon Xi, Wei Xu, Jessica Mei Kay Yang, Allan H. Young, Hannah Young, Peter P. Zandi, Hang Zhou, null HUNT All-In Psychiatry, Gulja Babadjanova, Lena Backlund, Susanne Bengesser, Douglas H.R. Blackwood, Vaughan J. Carr, Stanley Catts, Dimitris Dikeos, Bruno Etain, Panagiotis Ferentinos, Micha Gawlik, Elliot S. Gershon, Frans Henskens, Jan Hillert, Kyung Sue Hong, Christina M. Hultman, Kristian Hveem, Nakao Iwata, Assen V. Jablensky, George Kirov, Christine Lochner, Carmel Loughland, Carol A. Mathews, Francis J. McMahon, Patricia Michie, Bryan Mowry, Benjamin M. Neale, Caroline M. Nievergelt, Ketil J. Oedegaard, Tomas Olsson, Chris Pantelis, George P. Patrinos, Eva Z. Reininghaus, Takeo Saito, Ulrich Schall, Martin Schalling, Rodney J. Scott, Eystein Stordal, Arne E. Vaaler, Eduard Vieta, Irwin D. Waldman, John-Anker Zwart, John I. Nurnberger, Arianna Di Florio, Roger A.H. Adan, Tetsuya Ando, Harald Aschauer, Jessica H. Baker, Vladimir Bencko, Andreas Birgegård, Joseph M. Boden, Ilka Boehm, Claudette Boni, Vesna Boraska Perica, Katharina Buehren, Roland Burghardt, Laura Carlberg, Matteo Cassina, Maurizio Clementi, Roger D. Cone, Philippe Courtet, James J. Crowley, Unna N. Danner, Oliver S.P. Davis, Martina de Zwaan, George Dedoussis, Daniela Degortes, Janiece E. DeSocio, Danielle M. Dick, Christian Dina, Monika Dmitrzak-Weglarz, Elisa Docampo Martinez, Laramie E. Duncan, Karin Egberts, Morten Mattingsdal, Sara McDevitt, Ingrid Meulenbelt, Nadia Micali, James Mitchell, Karen Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Melissa A. Munn-Chernoff, Benedetta Nacmias, Marie Navratilova, Ioanna Ntalla, Julie K. O’Toole, Leonid Padyukov, Aarno Palotie, Jacques Pantel, Hana Papezova, Richard Parker, John F. Pearson, Stefan Ehrlich, Geòrgia Escaramís, Thomas Espeseth, Xavier Estivill, Anne Farmer, Angela Favaro, Krista Fischer, James A.B. Floyd, Manuel Föcker, Lenka Foretova, Monica Forzan, Christopher S. Franklin, Giovanni Gambaro, Johanna Giuranna, Paola Giusti-Rodríquez, Fragiskos Gonidakis, Scott Gordon, Monica Gratacos Mayora, Sébastien Guillaume, Ken B. Hanscombe, Konstantinos Hatzikotoulas, Johannes Hebebrand, Sietske G. Helder, Anjali K. Henders, Beate Herpertz-Dahlmann, Wolfgang Herzog, Anke Hinney, L. John Horwood, Christopher Hübel, Liselotte V. Petersen, Kirstin L. Purves, Anu Raevuori, Ted Reichborn-Kjennerud, Valdo Ricca, Samuli Ripatti, Franziska Ritschel, Marion Roberts, Filip Rybakowski, Paolo Santonastaso, André Scherag, Ulrike Schmidt, Nicholas J. Schork, Alexandra Schosser, Jochen Seitz, Lenka Slachtova, P. Eline Slagboom, Margarita C.T. Slof-Op ‘t Landt, Agnieszka Slopien, Nicole Soranzo, Sandro Sorbi, Lorraine Southam, Vidar W. Steen, Laura M. Huckins, James I. Hudson, Hartmut Imgart, Hidetoshi Inoko, Vladimir Janout, Jennifer Jordan, Antonio Julià, Gursharan Kalsi, Deborah Kaminská, Jaakko Kaprio, Leila Karhunen, Andreas Karwautz, Martien J.H. Kas, Martin A. Kennedy, Anna Keski-Rahkonen, Kirsty Kiezebrink, Youl-Ri Kim, Katherine M. Kirk, Lars Klareskog, Gun Peggy S. Knudsen, Janne T. Larsen, Stephanie Le Hellard, Virpi M. Leppä, Paul Lichtenstein, Bochao Danae Lin, Astri Lundervold, Jurjen Luykx, Mario Maj, Katrin Mannik, Sara Marsal, Garret D. Stuber, Jin P. Szatkiewicz, Ioanna Tachmazidou, Elena Tenconi, Alfonso Tortorella, Federica Tozzi, Artemis Tsitsika, Marta Tyszkiewicz-Nwafor, Konstantinos Tziouvas, Annemarie A. van Elburg, Eric F. van Furth, Tracey D. Wade, Gudrun Wagner, Esther Walton, H. Erich Wichmann, Elisabeth Widen, Shuyang Yao, Eleftheria Zeggini, Stephanie Zerwas, Stephan Zipfel, Martin Jungkunz, Lydie Dietl, Cornelia E. Schwarze, Norbert Dahmen, Björn H. Schott, Arian Mobascher, Silvia Crivelli, Michelle F. Dennis, Phillip D. Harvey, Bruce W. Carter, Jennifer E. Huffman, Daniel Jacobson, Ravi Madduri, Maren K. Olsen, John Pestian, J. Michael Gaziano, Sumitra Muralidhar, Rachel Ramoni, Jean Beckham, Kyong-Mi Chang, Christopher J. O’Donnell, Philip S. Tsao, James Breeling, Grant Huang, J.P. Casas Romero, Jennifer Moser, Stacey B. Whitbourne, Jessica V. Brewer, Mihaela Aslan, Todd Connor, Dean P. Argyres, Brady Stephens, Mary T. Brophy, Donald E. Humphries, Luis E. Selva, Nhan Do, Shahpoor Shayan, Kelly Cho, Saiju Pyarajan, Elizabeth Hauser, Yan Sun, Hongyu Zhao, Peter Wilson, Rachel McArdle, Louis Dellitalia, Kristin Mattocks, John Harley, Clement J. Zablocki, Jeffrey Whittle, Frank Jacono, Salvador Gutierrez, Gretchen Gibson, Kimberly Hammer, Laurence Kaminsky, Gerardo Villareal, Scott Kinlay, Junzhe Xu, Mark Hamner, Roy Mathew, Sujata Bhushan, Pran Iruvanti, Michael Godschalk, Zuhair Ballas, Douglas Ivins, Stephen Mastorides, Jonathan Moorman, Saib Gappy, Jon Klein, Nora Ratcliffe, Hermes Florez, Olaoluwa Okusaga, Maureen Murdoch, Peruvemba Sriram, Shing Shing Yeh, Neeraj Tandon, Darshana Jhala, Samuel Aguayo, David Cohen, Satish Sharma, Suthat Liangpunsakul, Kris Ann Oursler, Mary Whooley, Sunil Ahuja, Joseph Constans, Paul Meyer, Jennifer Greco, Michael Rauchman, Richard Servatius, Melinda Gaddy, Agnes Wallbom, Timothy Morgan, Todd Stapley, Scott Sherman, George Ross, Philip Tsao, Patrick Strollo, Edward Boyko, Laurence Meyer, Samir Gupta, Mostaqul Huq, Joseph Fayad, Adriana Hung, Jack Lichy, Robin Hurley, Brooks Robey, Robert Striker, Dietl, Lydie, Schwarze, Cornelia E., Dahmen, Norbert, Schott, Björn H., Nöthen, Markus M., Ripke, Stephan, Mobascher, Arian, Rujescu, Dan, Lieb, Klaus, Roepke, Stefan, Schmahl, Christian, Bohus, Martin, Rietschel, Marcella, Crivelli, Silvia, Dennis, Michelle F., Harvey, Phillip D., Carter, Bruce W., Huffman, Jennifer E., Jacobson, Daniel, Madduri, Ravi, Olsen, Maren K., Pestian, John, Gaziano, J. Michael, Muralidhar, Sumitra, Ramoni, Rachel, Beckham, Jean, Chang, Kyong-Mi, O'Donnell, Christopher J., Tsao, Philip S., Breeling, James, Huang, Grant, Romero, J. P. Casas, Moser, Jennifer, Whitbourne, Stacey B., Brewer, Jessica V., Aslan, Mihaela, Connor, Todd, Argyres, Dean P., Stephens, Brady, Brophy, Mary T., Humphries, Donald E., Selva, Luis E., Do, Nhan, Shayan, Shahpoor, Cho, Kelly, Pyarajan, Saiju, Hauser, Elizabeth, Sun, Yan, Zhao, Hongyu, Wilson, Peter, McArdle, Rachel, Dellitalia, Louis, Mattocks, Kristin, Harley, John, Zablocki, Clement J., Whittle, Jeffrey, Jacono, Frank, Gutierrez, Salvador, Gibson, Gretchen, Hammer, Kimberly, Kaminsky, Laurence, Villareal, Gerardo, Kinlay, Scott, Xu, Junzhe, Hamner, Mark, Mathew, Roy, Bhushan, Sujata, Iruvanti, Pran, Godschalk, Michael, Ballas, Zuhair, Ivins, Douglas, Mastorides, Stephen, Moorman, Jonathan, Gappy, Saib, Klein, Jon, Ratcliffe, Nora, Florez, Hermes, Okusaga, Olaoluwa, Murdoch, Maureen, Sriram, Peruvemba, Yeh, Shing Shing, Tandon, Neeraj, Jhala, Darshana, Aguayo, Samuel, Cohen, David, Sharma, Satish, Liangpunsakul, Suthat, Oursler, Kris Ann, Whooley, Mary, Ahuja, Sunil, Constans, Joseph, Meyer, Paul, Greco, Jennifer, Rauchman, Michael, Servatius, Richard, Gaddy, Melinda, Wallbom, Agnes, Morgan, Timothy, Stapley, Todd, Sherman, Scott, Ross, George, Tsao, Philip, Strollo, Patrick, Boyko, Edward, Meyer, Laurence, Gupta, Samir, Huq, Mostaqul, Fayad, Joseph, Hung, Adriana, Lichy, Jack, Hurley, Robin, Robey, Brooks, Striker, Robert, Wray, Naomi R., Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M., Abdellaoui, Abdel, Adams, Mark J., Agerbo, Esben, Air, Tracy M., Andlauer, Till F. M., Bacanu, Silviu-Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T. F., Bigdeli, Tim B., Binder, Elisabeth B., Bryois, Julien, Buttenschøn, Henriette N., Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni-Kim, Coleman, Jonathan R. I., Colodro-Conde, Lucía, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E., Davies, Gail, Degenhardt, Franziska, Derks, Eske M., Direk, Nese, Dolan, Conor V., Dunn, Erin C., Eley, Thalia C., Escott-Price, Valentina, Hassan Kiadeh, Farnush Farhadi, Finucane, Hilary K., Foo, Jerome C., Forstner, Andreas J., Frank, Josef, Gaspar, Héléna A., Gill, Michael, Goes, Fernando S., Gordon, Scott D., Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Witt, Stephanie H., Wu, Yang, Xi, Hualin S., Yang, Jian, Zhang, Futao, Arolt, Volker, Baune, Bernhard T., Berger, Klaus, Boomsma, Dorret I., Cichon, Sven, Dannlowski, Udo, de Geus, E. J. C., DePaulo, J. Raymond, Domenici, Enrico, Domschke, Katharina, Esko, Tõnu, Grabe, Hans J., Hamilton, Steven P., Grove, Jakob, Hall, Lynsey S., Hansen, Christine Søholm, Hansen, Thomas F., Herms, Stefan, Hickie, Ian B., Hoffmann, Per, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Hougaard, David M., Howard, David M., Ising, Marcus, Jansen, Rick, Jones, Ian, Jones, Lisa A., Jorgenson, Eric, Knowles, James A., Kohane, Isaac S., Kraft, Julia, Kretzschmar, Warren W., Kutalik, Zoltán, Li, Yihan, Lind, Penelope A., MacIntyre, Donald J., MacKinnon, Dean F., Maier, Robert M., Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E., Mehta, Divya, Middeldorp, Christel M., Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mondimore, Francis M., Montgomery, Grant W., Mostafavi, Sara, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G., Nyholt, Dale R., O'Reilly, Paul F., Oskarsson, Hogni, Hayward, Caroline, Heath, Andrew C., Kendler, Kenneth S., Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S., Lucae, Susanne, Madden, Pamela A. F., Magnusson, Patrik K., Martin, Nicholas G., McIntosh, Andrew M., Metspalu, Andres, Mors, Ole, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Nordentoft, Merete, O'Donovan, Michael C., Paciga, Sara A., Pedersen, Nancy L., Owen, Michael J., Painter, Jodie N., Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Peterson, Roseann E., Peyrot, Wouter J., Pistis, Giorgio, Posthuma, Danielle, Quiroz, Jorge A., Qvist, Per, Rice, John P., Riley, Brien P., Rivera, Margarita, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C., Shen, Ling, Shi, Jianxin, Shyn, Stanley I., Sigurdsson, Engilbert, Sinnamon, Grant C. B., Smit, Johannes H., Smith, Daniel J., Stefansson, Hreinn, Steinberg, Stacy, Streit, Fabian, Strohmaier, Jana, Tansey, Katherine E., Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A., Thorgeirsson, Thorgeir E., Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, André G., Umbricht, Daniel, Van der Auwera, Sandra, van Hemert, Albert M., Viktorin, Alexander, Visscher, Peter M., Wang, Yunpeng, Webb, Bradley T., Penninx, Brenda W. J. H., Perlis, Roy H., Porteous, David J., Potash, James B., Preisig, Martin, Schaefer, Catherine, Schulze, Thomas G., Smoller, Jordan W., Stefansson, Kari, Tiemeier, Henning, Uher, Rudolf, Völzke, Henry, Weissman, Myrna M., Werge, Thomas, Lewis, Cathryn M., Levinson, Douglas F., Breen, Gerome, Børglum, Anders D., Sullivan, Patrick F., O'Connell, Kevin S., Coombes, Brandon, Qiao, Zhen, Als, Thomas D., Børte, Sigrid, Charney, Alexander W., Drange, Ole Kristian, Gandal, Michael J., Hagenaars, Saskia P., Ikeda, Masashi, Kamitaki, Nolan, Kim, Minsoo, Krebs, Kristi, Panagiotaropoulou, Georgia, Schilder, Brian M., Sloofman, Laura G., Winsvold, Bendik S., Won, Hong-Hee, Abramova, Liliya, Adorjan, Kristina, Al Eissa, Mariam, Albani, Diego, Alliey-Rodriguez, Ney, Anjorin, Adebayo, Antilla, Verneri, Antoniou, Anastasia, Awasthi, Swapnil, Baek, Ji Hyun, Bass, Nicholas, Bauer, Michael, Beins, Eva C., Bergen, Sarah E., Birner, Armin, Bøen, Erlend, Boks, Marco P., Bosch, Rosa, Brum, Murielle, Brumpton, Ben M., Brunkhorst-Kanaan, Nathalie, Budde, Monika, Byerley, William, Cairns, Murray, Casas, Miquel, Cervantes, Pablo, Cruceanu, Cristiana, Cuellar-Barboza, Alfredo, Cunningham, Julie, Curtis, David, Czerski, Piotr M., Dale, Anders M., Dalkner, Nina, David, Friederike S., Djurovic, Srdjan, Dobbyn, Amanda L., Douzenis, Athanassios, Elvsåshagen, Torbjørn, Ferrier, I. Nicol, Fiorentino, Alessia, Foroud, Tatiana M., Forty, Liz, Frei, Oleksandr, Freimer, Nelson B., Frisén, Louise, Gade, Katrin, Garnham, Julie, Gelernter, Joel, Gizer, Ian R., Gordon-Smith, Katherine, Greenwood, Tiffany A., Guzman-Parra, José, Ha, Kyooseob, Haraldsson, Magnus, Hautzinger, Martin, Heilbronner, Urs, Hellgren, Dennis, Holmans, Peter A., Huckins, Laura, Jamain, Stéphane, Johnson, Jessica S., Kalman, Janos L., Kamatani, Yoichiro, Kennedy, James L., Kittel-Schneider, Sarah, Kogevinas, Manolis, Koromina, Maria, Kranz, Thorsten M., Kranzler, Henry R., Kubo, Michiaki, Kupka, Ralph, Kushner, Steven A., Lavebratt, Catharina, Lawrence, Jacob, Leber, Markus, Lee, Heon-Jeong, Lee, Phil H., Levy, Shawn E., Lewis, Catrin, Liao, Calwing, Lundberg, Martin, Magnusson, Sigurdur H., Maihofer, Adam, Malaspina, Dolores, Maratou, Eirini, Martinsson, Lina, McGregor, Nathaniel W., McKay, James D., Medeiros, Helena, Millischer, Vincent, Moran, Jennifer L., Morris, Derek W., Mühleisen, Thomas W., O'Brien, Niamh, O'Donovan, Claire, Olde Loohuis, Loes M., Oruc, Lilijana, Papiol, Sergi, Pardiñas, Antonio F., Perry, Amy, Pfennig, Andrea, Porichi, Evgenia, Quested, Digby, Raj, Towfique, Rapaport, Mark H., Regeer, Eline J., Rivas, Fabio, Roth, Julian, Roussos, Panos, Ruderfer, Douglas M., Sánchez-Mora, Cristina, Senner, Fanny, Sharp, Sally, Shilling, Paul D., Sirignano, Lea, Slaney, Claire, Smeland, Olav B., Sobell, Janet L., Artigas, Maria Soler, Spijker, Anne T., Stein, Dan J., Strauss, John S., Świątkowska, Beata, Terao, Chikashi, Toma, Claudio, Tooney, Paul, Tsermpini, Evangelia-Eirini, Vawter, Marquis P., Vedder, Helmut, Walters, James T. R., Xi, Simon, Xu, Wei, Kay Yang, Jessica Mei, Young, Allan H., Young, Hannah, Zandi, Peter P., Zhou, Hang, Zillich, Lea, Adolfsson, Rolf, Agartz, Ingrid, Alda, Martin, Alfredsson, Lars, Babadjanova, Gulja, Backlund, Lena, Bellivier, Frank, Bengesser, Susanne, Berrettini, Wade H., Blackwood, Douglas H. R., Boehnke, Michael, Carr, Vaughan J., Catts, Stanley, Corvin, Aiden, Craddock, Nicholas, Dikeos, Dimitris, Etain, Bruno, Ferentinos, Panagiotis, Frye, Mark, Fullerton, Janice M., Gawlik, Micha, Gershon, Elliot S., Green, Melissa J., Grigoroiu-Serbanescu, Maria, Hauser, Joanna, Henskens, Frans, Hillert, Jan, Hong, Kyung Sue, Hultman, Christina M., Hveem, Kristian, Iwata, Nakao, Jablensky, Assen V., Kahn, René S., Kelsoe, John R., Kirov, George, Landén, Mikael, Leboyer, Marion, Lissowska, Jolanta, Lochner, Christine, Loughland, Carmel, Mathews, Carol A., Mayoral, Fermin, McElroy, Susan L., McMahon, Francis J., Melle, Ingrid, Michie, Patricia, Mitchell, Philip B., Morken, Gunnar, Mowry, Bryan, Myers, Richard M., Neale, Benjamin M., Nievergelt, Caroline M., Oedegaard, Ketil J., Olsson, Tomas, Pantelis, Chris, Pato, Carlos, Pato, Michele T., Patrinos, George P., Ramos-Quiroga, Josep Antoni, Reif, Andreas, Reininghaus, Eva Z., Ribasés, Marta, Rouleau, Guy A., Saito, Takeo, Schall, Ulrich, Schalling, Martin, Schofield, Peter R., Scott, Laura J., Scott, Rodney J., Serretti, Alessandro, Weickert, Cynthia Shannon, Stordal, Eystein, Turecki, Gustavo, Vaaler, Arne E., Vieta, Eduard, Vincent, John B., Waldman, Irwin D., Weickert, Thomas W., Zwart, John-Anker, Biernacka, Joanna M., Nurnberger, John I., Edenberg, Howard J., Stahl, Eli A., McQuillin, Andrew, Di Florio, Arianna, Ophoff, Roel A., Andreassen, Ole A., Adan, Roger A. H., Ando, Tetsuya, Aschauer, Harald, Baker, Jessica H., Bencko, Vladimir, Bergen, Andrew W., Birgegård, Andreas, Boden, Joseph M., Boehm, Ilka, Boni, Claudette, Perica, Vesna Boraska, Brandt, Harry, Buehren, Katharina, Bulik, Cynthia M., Burghardt, Roland, Carlberg, Laura, Cassina, Matteo, Clementi, Maurizio, Cone, Roger D., Courtet, Philippe, Crawford, Steven, Crow, Scott, Crowley, James J., Danner, Unna N., Davis, Oliver S. P., de Zwaan, Martina, Dedoussis, George, Degortes, Daniela, DeSocio, Janiece E., Dick, Danielle M., Dina, Christian, Dmitrzak-Weglarz, Monika, Martinez, Elisa Docampo, Duncan, Laramie E., Egberts, Karin, Marshall, Christian R., Mattingsdal, Morten, McDevitt, Sara, Meulenbelt, Ingrid, Micali, Nadia, Mitchell, James, Mitchell, Karen, Monteleone, Palmiero, Monteleone, Alessio Maria, Munn-Chernoff, Melissa A., Nacmias, Benedetta, Navratilova, Marie, Ntalla, Ioanna, Olsen, Catherine M., O'Toole, Julie K., Padyukov, Leonid, Palotie, Aarno, Pantel, Jacques, Papezova, Hana, Parker, Richard, Pearson, John F., Ehrlich, Stefan, Escaramís, Geòrgia, Espeseth, Thomas, Estivill, Xavier, Farmer, Anne, Favaro, Angela, Fernández-Aranda, Fernando, Fichter, Manfred M., Fischer, Krista, Floyd, James A. B., Föcker, Manuel, Foretova, Lenka, Forzan, Monica, Franklin, Christopher S., Gallinger, Steven, Gambaro, Giovanni, Giegling, Ina, Giuranna, Johanna, Giusti-Rodríquez, Paola, Gonidakis, Fragiskos, Gordon, Scott, Gorwood, Philip, Mayora, Monica Gratacos, Guillaume, Sébastien, Guo, Yiran, Hakonarson, Hakon, Halmi, Katherine A., Hanscombe, Ken B., Hatzikotoulas, Konstantinos, Hebebrand, Johannes, Helder, Sietske G., Henders, Anjali K., Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Hinney, Anke, Horwood, L. John, Hübel, Christopher, Petersen, Liselotte V., Pinto, Dalila, Purves, Kirstin L., Raevuori, Anu, Ramoz, Nicolas, Reichborn-Kjennerud, Ted, Ricca, Valdo, Ripatti, Samuli, Ritschel, Franziska, Roberts, Marion, Rybakowski, Filip, Santonastaso, Paolo, Scherag, André, Scherer, Stephen W., Schmidt, Ulrike, Schork, Nicholas J., Schosser, Alexandra, Seitz, Jochen, Slachtova, Lenka, Slagboom, P. Eline, Slof-Op 't Landt, Margarita C. T., Slopien, Agnieszka, Soranzo, Nicole, Sorbi, Sandro, Southam, Lorraine, Steen, Vidar W., Strober, Michael, Huckins, Laura M., Hudson, James I., Imgart, Hartmut, Inoko, Hidetoshi, Janout, Vladimir, Jiménez-Murcia, Susana, Johnson, Craig, Jordan, Jennifer, Julià, Antonio, Kalsi, Gursharan, Kaminská, Deborah, Kaplan, Allan S., Kaprio, Jaakko, Karhunen, Leila, Karwautz, Andreas, Kas, Martien J. H., Kaye, Walter H., Kennedy, Martin A., Keski-Rahkonen, Anna, Kiezebrink, Kirsty, Kim, Youl-Ri, Kirk, Katherine M., Klareskog, Lars, Klump, Kelly L., Knudsen, Gun Peggy S., Larsen, Janne T., Le Hellard, Stephanie, Leppä, Virpi M., Li, Dong, Lichtenstein, Paul, Lilenfeld, Lisa, Lin, Bochao Danae, Lundervold, Astri, Luykx, Jurjen, Magistretti, Pierre J., Maj, Mario, Mannik, Katrin, Marsal, Sara, Stuber, Garret D., Szatkiewicz, Jin P., Tachmazidou, Ioanna, Tenconi, Elena, Thornton, Laura M., Tortorella, Alfonso, Tozzi, Federica, Treasure, Janet, Tsitsika, Artemis, Tyszkiewicz-Nwafor, Marta, Tziouvas, Konstantinos, van Elburg, Annemarie A., van Furth, Eric F., Wade, Tracey D., Wagner, Gudrun, Walton, Esther, Watson, Hunna J., Whiteman, David C., Wichmann, H. Erich, Widen, Elisabeth, Woodside, D. Blake, Yao, Shuyang, Yilmaz, Zeynep, Zeggini, Eleftheria, Zerwas, Stephanie, Zipfel, Stephan, Jungkunz, Martin, Mullins, N., Kang, J., Campos, A. I., Coleman, J. R. I., Edwards, A. C., Galfalvy, H., Levey, D. F., Lori, A., Shabalin, A., Starnawska, A., Su, M. -H., Watson, H. J., Adams, M., Awasthi, S., Gandal, M., Hafferty, J. D., Hishimoto, A., Kim, M., Okazaki, S., Otsuka, I., Ripke, S., Ware, E. B., Bergen, A. W., Berrettini, W. H., Bohus, M., Brandt, H., Chang, X., Chen, W. J., Chen, H. -C., Crawford, S., Crow, S., Diblasi, E., Duriez, P., Fernandez-Aranda, F., Fichter, M. M., Gallinger, S., Glatt, S. J., Gorwood, P., Guo, Y., Hakonarson, H., Halmi, K. A., Hwu, H. -G., Jain, S., Jamain, S., Jimenez-Murcia, S., Johnson, C., Kaplan, A. S., Kaye, W. H., Keel, P. K., Kennedy, J. L., Klump, K. L., Li, D., Liao, S. -C., Lieb, K., Lilenfeld, L., Liu, C. -M., Magistretti, P. J., Marshall, C. R., Mitchell, J. E., Monson, E. T., Myers, R. M., Pinto, D., Powers, A., Ramoz, N., Roepke, S., Rozanov, V., Scherer, S. W., Schmahl, C., Sokolowski, M., Strober, M., Thornton, L. M., Treasure, J., Tsuang, M. T., Witt, S. H., Woodside, D. B., Yilmaz, Z., Zillich, L., Adolfsson, R., Agartz, I., Air, T. M., Alda, M., Alfredsson, L., Andreassen, O. A., Anjorin, A., Appadurai, V., Soler Artigas, M., Van der Auwera, S., Azevedo, M. H., Bass, N., Bau, C. H. D., Baune, B. T., Bellivier, F., Berger, K., Biernacka, J. M., Bigdeli, T. B., Binder, E. B., Boehnke, M., Boks, M. P., Bosch, R., Braff, D. L., Bryant, R., Budde, M., Byrne, E. M., Cahn, W., Casas, M., Castelao, E., Cervilla, J. A., Chaumette, B., Cichon, S., Corvin, A., Craddock, N., Craig, D., Degenhardt, F., Djurovic, S., Edenberg, H. J., Fanous, A. H., Foo, J. C., Forstner, A. J., Frye, M., Fullerton, J. M., Gatt, J. M., Gejman, P. V., Giegling, I., Grabe, H. J., Green, M. J., Grevet, E. H., Grigoroiu-Serbanescu, M., Gutierrez, B., Guzman-Parra, J., Hamilton, S. P., Hamshere, M. L., Hartmann, A., Hauser, J., Heilmann-Heimbach, S., Hoffmann, P., Ising, M., Jones, I., Jones, L. A., Jonsson, L., Kahn, R. S., Kelsoe, J. R., Kendler, K. S., Kloiber, S., Koenen, K. C., Kogevinas, M., Konte, B., Krebs, M. -O., Landen, M., Lawrence, J., Leboyer, M., Lee, P. H., Levinson, D. F., Liao, C., Lissowska, J., Lucae, S., Mayoral, F., Mcelroy, S. L., Mcgrath, P., Mcguffin, P., Mcquillin, A., Medland, S. E., Mehta, D., Melle, I., Milaneschi, Y., Mitchell, P. B., Molina, E., Morken, G., Mortensen, P. B., Muller-Myhsok, B., Nievergelt, C., Nimgaonkar, V., Nothen, M. M., O'Donovan, M. C., Ophoff, R. A., Owen, M. J., Pato, C., Pato, M. T., Penninx, B. W. J. H., Pimm, J., Pistis, G., Potash, J. B., Power, R. A., Preisig, M., Quested, D., Ramos-Quiroga, J. A., Reif, A., Ribases, M., Richarte, V., Rietschel, M., Rivera, M., Roberts, A., Roberts, G., Rouleau, G. A., Rovaris, D. L., Rujescu, D., Sanchez-Mora, C., Sanders, A. R., Schofield, P. R., Schulze, T. G., Scott, L. J., Serretti, A., Shi, J., Shyn, S. I., Sirignano, L., Sklar, P., Smeland, O. B., Smoller, J. W., Sonuga-Barke, E. J. S., Spalletta, G., Strauss, J. S., Swiatkowska, B., Trzaskowski, M., Turecki, G., Vilar-Ribo, L., Vincent, J. B., Volzke, H., Walters, J. T. R., Shannon Weickert, C., Weickert, T. W., Weissman, M. M., Williams, L. M., Wray, N. R., Zai, C. C., Ashley-Koch, A. E., Beckham, J. C., Hauser, E. R., Hauser, M. A., Kimbrel, N. A., Lindquist, J. H., Mcmahon, B., Oslin, D. W., Qin, X., Mattheisen, M., Abdellaoui, A., Adams, M. J., Agerbo, E., Andlauer, T. F. M., Bacanu, S. -A., Baekvad-Hansen, M., Beekman, A. T. F., Bryois, J., Buttenschon, H. N., Bybjerg-Grauholm, J., Cai, N., Christensen, J. H., Clarke, T. -K., Colodro-Conde, L., Couvy-Duchesne, B., Crawford, G. E., Davies, G., Derks, E. M., Direk, N., Dolan, C. V., Dunn, E. C., Eley, T. C., Escott-Price, V., Hassan Kiadeh, F. F., Finucane, H. K., Frank, J., Gaspar, H. A., Gill, M., Goes, F. S., Gordon, S. D., Weinsheimer, S. M., Wellmann, J., Willemsen, G., Wu, Y., Xi, H. S., Yang, J., Zhang, F., Arolt, V., Boomsma, D. I., Dannlowski, U., Depaulo, J. R., Domenici, E., Domschke, K., Esko, T., Grove, J., Hall, L. S., Hansen, C. S., Hansen, T. F., Herms, S., Hickie, I. B., Homuth, G., Horn, C., Hottenga, J. -J., Hougaard, D. M., Howard, D. M., Jansen, R., Jorgenson, E., Knowles, J. A., Kohane, I. S., Kraft, J., Kretzschmar, W. W., Kutalik, Z., Li, Y., Lind, P. A., Macintyre, D. J., Mackinnon, D. F., Maier, R. M., Maier, W., Marchini, J., Mbarek, H., Middeldorp, C. M., Mihailov, E., Milani, L., Mondimore, F. M., Montgomery, G. W., Mostafavi, S., Nauck, M., Ng, B., Nivard, M. G., Nyholt, D. R., O'Reilly, P. F., Oskarsson, H., Hayward, C., Heath, A. C., Lewis, G., Li, Q. S., Madden, P. A. F., Magnusson, P. K., Martin, N. G., Mcintosh, A. M., Metspalu, A., Mors, O., Nordentoft, M., Paciga, S. A., Pedersen, N. L., Painter, J. N., Pedersen, C. B., Pedersen, M. G., Peterson, R. E., Peyrot, W. J., Posthuma, D., Quiroz, J. A., Qvist, P., Rice, J. P., Riley, B. P., Mirza, S. S., Schoevers, R., Schulte, E. C., Shen, L., Sigurdsson, E., Sinnamon, G. C. B., Smit, J. H., Smith, D. J., Stefansson, H., Steinberg, S., Streit, F., Strohmaier, J., Tansey, K. E., Teismann, H., Teumer, A., Thompson, W., Thomson, P. A., Thorgeirsson, T. E., Traylor, M., Treutlein, J., Trubetskoy, V., Uitterlinden, A. G., Umbricht, D., der Auwera, S. V., van Hemert, A. M., Viktorin, A., Visscher, P. M., Wang, Y., Webb, B. T., Perlis, R. H., Porteous, D. J., Schaefer, C., Stefansson, K., Tiemeier, H., Uher, R., Werge, T., Lewis, C. M., Breen, G., Borglum, A. D., Sullivan, P. F., O'Connell, K. S., Coombes, B., Qiao, Z., Als, T. D., Borte, S., Charney, A. W., Drange, O. K., Gandal, M. J., Hagenaars, S. P., Ikeda, M., Kamitaki, N., Krebs, K., Panagiotaropoulou, G., Schilder, B. M., Sloofman, L. G., Winsvold, B. S., Won, H. -H., Abramova, L., Adorjan, K., Al Eissa, M., Albani, D., Alliey-Rodriguez, N., Antilla, V., Antoniou, A., Baek, J. H., Bauer, M., Beins, E. C., Bergen, S. E., Birner, A., Boen, E., Brum, M., Brumpton, B. M., Brunkhorst-Kanaan, N., Byerley, W., Cairns, M., Cervantes, P., Cruceanu, C., Cuellar-Barboza, A., Cunningham, J., Curtis, D., Czerski, P. M., Dale, A. M., Dalkner, N., David, F. S., Dobbyn, A. L., Douzenis, A., Elvsashagen, T., Ferrier, I. N., Fiorentino, A., Foroud, T. M., Forty, L., Frei, O., Freimer, N. B., Frisen, L., Gade, K., Garnham, J., Gelernter, J., Gizer, I. R., Gordon-Smith, K., Greenwood, T. A., Ha, K., Haraldsson, M., Hautzinger, M., Heilbronner, U., Hellgren, D., Holmans, P. A., Huckins, L., Johnson, J. S., Kalman, J. L., Kamatani, Y., Kittel-Schneider, S., Koromina, M., Kranz, T. M., Kranzler, H. R., Kubo, M., Kupka, R., Kushner, S. A., Lavebratt, C., Leber, M., Lee, H. -J., Levy, S. E., Lewis, C., Lundberg, M., Magnusson, S. H., Maihofer, A., Malaspina, D., Maratou, E., Martinsson, L., Mcgregor, N. W., Mckay, J. D., Medeiros, H., Millischer, V., Moran, J. L., Morris, D. W., Muhleisen, T. W., O'Brien, N., O'Donovan, C., Olde Loohuis, L. M., Oruc, L., Papiol, S., Pardinas, A. F., Perry, A., Pfennig, A., Porichi, E., Raj, T., Rapaport, M. H., Regeer, E. J., Rivas, F., Roth, J., Roussos, P., Ruderfer, D. M., Senner, F., Sharp, S., Shilling, P. D., Slaney, C., Sobell, J. L., Artigas, M. S., Spijker, A. T., Stein, D. J., Terao, C., Toma, C., Tooney, P., Tsermpini, E. -E., Vawter, M. P., Vedder, H., Xi, S., Xu, W., Kay Yang, J. M., Young, A. H., Young, H., Zandi, P. P., Zhou, H., HUNT All-In, Psychiatry, Babadjanova, G., Backlund, L., Bengesser, S., Blackwood, D. H. R., Carr, V. J., Catts, S., Dikeos, D., Etain, B., Ferentinos, P., Gawlik, M., Gershon, E. S., Henskens, F., Hillert, J., Hong, K. S., Hultman, C. M., Hveem, K., Iwata, N., Jablensky, A. V., Kirov, G., Lochner, C., Loughland, C., Mathews, C. A., Mcmahon, F. J., Michie, P., Mowry, B., Neale, B. M., Nievergelt, C. M., Oedegaard, K. J., Olsson, T., Pantelis, C., Patrinos, G. P., Reininghaus, E. Z., Saito, T., Schall, U., Schalling, M., Scott, R. J., Weickert, C. S., Stordal, E., Vaaler, A. E., Vieta, E., Waldman, I. D., Zwart, J. -A., Nurnberger, J. I., Stahl, E. A., Di Florio, A., Adan, R. A. H., Ando, T., Aschauer, H., Baker, J. H., Bencko, V., Birgegard, A., Boden, J. M., Boehm, I., Boni, C., Perica, V. B., Buehren, K., Bulik, C. M., Burghardt, R., Carlberg, L., Cassina, M., Clementi, M., Cone, R. D., Courtet, P., Crowley, J. J., Danner, U. N., Davis, O. S. P., de Zwaan, M., Dedoussis, G., Degortes, D., Desocio, J. E., Dick, D. M., Dina, C., Dmitrzak-Weglarz, M., Martinez, E. D., Duncan, L. E., Egberts, K., Mattingsdal, M., Mcdevitt, S., Meulenbelt, I., Micali, N., Mitchell, J., Mitchell, K., Monteleone, P., Monteleone, A. M., Munn-Chernoff, M. A., Nacmias, B., Navratilova, M., Ntalla, I., Olsen, C. M., O'Toole, J. K., Padyukov, L., Palotie, A., Pantel, J., Papezova, H., Parker, R., Pearson, J. F., Ehrlich, S., Escaramis, G., Espeseth, T., Estivill, X., Farmer, A., Favaro, A., Fischer, K., Floyd, J. A. B., Focker, M., Foretova, L., Forzan, M., Franklin, C. S., Gambaro, G., Giuranna, J., Giusti-Rodriquez, P., Gonidakis, F., Gordon, S., Mayora, M. G., Guillaume, S., Hanscombe, K. B., Hatzikotoulas, K., Hebebrand, J., Helder, S. G., Henders, A. K., Herpertz-Dahlmann, B., Herzog, W., Hinney, A., Horwood, L. J., Hubel, C., Petersen, L. V., Purves, K. L., Raevuori, A., Reichborn-Kjennerud, T., Ricca, V., Ripatti, S., Ritschel, F., Roberts, M., Rybakowski, F., Santonastaso, P., Scherag, A., Schmidt, U., Schork, N. J., Schosser, A., Seitz, J., Slachtova, L., Slagboom, P. E., Slof-Op 't Landt, M. C. T., Slopien, A., Soranzo, N., Sorbi, S., Southam, L., Steen, V. W., Huckins, L. M., Hudson, J. I., Imgart, H., Inoko, H., Janout, V., Jordan, J., Julia, A., Kalsi, G., Kaminska, D., Kaprio, J., Karhunen, L., Karwautz, A., Kas, M. J. H., Kennedy, M. A., Keski-Rahkonen, A., Kiezebrink, K., Kim, Y. -R., Kirk, K. M., Klareskog, L., Knudsen, G. P. S., Larsen, J. T., Le Hellard, S., Leppa, V. M., Lichtenstein, P., Lin, B. D., Lundervold, A., Luykx, J., Maj, M., Mannik, K., Marsal, S., Stuber, G. D., Szatkiewicz, J. P., Tachmazidou, I., Tenconi, E., Tortorella, A., Tozzi, F., Tsitsika, A., Tyszkiewicz-Nwafor, M., Tziouvas, K., van Elburg, A. A., van Furth, E. F., Wade, T. D., Wagner, G., Walton, E., Whiteman, D. C., Wichmann, H. E., Widen, E., Yao, S., Zeggini, E., Zerwas, S., Zipfel, S., Jungkunz, M., Dietl, L., Schwarze, C. E., Dahmen, N., Schott, B. H., Mobascher, A., Crivelli, S., Dennis, M. F., Harvey, P. D., Carter, B. W., Huffman, J. E., Jacobson, D., Madduri, R., Olsen, M. K., Pestian, J., Gaziano, J. M., Muralidhar, S., Ramoni, R., Beckham, J., Chang, K. -M., O'Donnell, C. J., Tsao, P. S., Breeling, J., Huang, G., Romero, J. P. C., Moser, J., Whitbourne, S. B., Brewer, J. V., Aslan, M., Connor, T., Argyres, D. P., Stephens, B., Brophy, M. T., Humphries, D. E., Selva, L. E., Do, N., Shayan, S., Cho, K., Pyarajan, S., Hauser, E., Sun, Y., Zhao, H., Wilson, P., Mcardle, R., Dellitalia, L., Mattocks, K., Harley, J., Zablocki, C. J., Whittle, J., Jacono, F., Gutierrez, S., Gibson, G., Hammer, K., Kaminsky, L., Villareal, G., Kinlay, S., Xu, J., Hamner, M., Mathew, R., Bhushan, S., Iruvanti, P., Godschalk, M., Ballas, Z., Ivins, D., Mastorides, S., Moorman, J., Gappy, S., Klein, J., Ratcliffe, N., Florez, H., Okusaga, O., Murdoch, M., Sriram, P., Yeh, S. S., Tandon, N., Jhala, D., Aguayo, S., Cohen, D., Sharma, S., Liangpunsakul, S., Oursler, K. A., Whooley, M., Ahuja, S., Constans, J., Meyer, P., Greco, J., Rauchman, M., Servatius, R., Gaddy, M., Wallbom, A., Morgan, T., Stapley, T., Sherman, S., Ross, G., Tsao, P., Strollo, P., Boyko, E., Meyer, L., Gupta, S., Huq, M., Fayad, J., Hung, A., Lichy, J., Hurley, R., Robey, B., Striker, R., Erlangsen, A., Kessler, R. C., Porteous, D., Ursano, R. J., Wasserman, D., Coon, H., Demontis, D., Docherty, A. R., Kuo, P. -H., Mann, J. J., Renteria, M. E., Stein, M. B., Willour, V., Psychiatry, Biological Psychology, APH - Methodology, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, AMS - Sports, AMS - Ageing & Vitality, APH - Personalized Medicine, Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Institute for Molecular Medicine Finland, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, HUS Psychiatry, Department of Public Health, Clinicum, Nuorisopsykiatria, Faculty Common Matters (Faculty of Social Sciences), Samuli Olli Ripatti / Principal Investigator, Complex Disease Genetics, Biostatistics Helsinki, Anna Keski-Rahkonen / Principal Investigator, Elisabeth Ingrid Maria Widen / Principal Investigator, Genomic Discoveries and Clinical Translation, Internal medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Mullins N., Kang J., Campos A.I., Coleman J.R.I., Edwards A.C., Galfalvy H., Levey D.F., Lori A., Shabalin A., Starnawska A., Su M.-H., Watson H.J., Adams M., Awasthi S., Gandal M., Hafferty J.D., Hishimoto A., Kim M., Okazaki S., Otsuka I., Ripke S., Ware E.B., Bergen A.W., Berrettini W.H., Bohus M., Brandt H., Chang X., Chen W.J., Chen H.-C., Crawford S., Crow S., DiBlasi E., Duriez P., Fernandez-Aranda F., Fichter M.M., Gallinger S., Glatt S.J., Gorwood P., Guo Y., Hakonarson H., Halmi K.A., Hwu H.-G., Jain S., Jamain S., Jimenez-Murcia S., Johnson C., Kaplan A.S., Kaye W.H., Keel P.K., Kennedy J.L., Klump K.L., Li D., Liao S.-C., Lieb K., Lilenfeld L., Liu C.-M., Magistretti P.J., Marshall C.R., Mitchell J.E., Monson E.T., Myers R.M., Pinto D., Powers A., Ramoz N., Roepke S., Rozanov V., Scherer S.W., Schmahl C., Sokolowski M., Strober M., Thornton L.M., Treasure J., Tsuang M.T., Witt S.H., Woodside D.B., Yilmaz Z., Zillich L., Adolfsson R., Agartz I., Air T.M., Alda M., Alfredsson L., Andreassen O.A., Anjorin A., Appadurai V., Soler Artigas M., Van der Auwera S., Azevedo M.H., Bass N., Bau C.H.D., Baune B.T., Bellivier F., Berger K., Biernacka J.M., Bigdeli T.B., Binder E.B., Boehnke M., Boks M.P., Bosch R., Braff D.L., Bryant R., Budde M., Byrne E.M., Cahn W., Casas M., Castelao E., Cervilla J.A., Chaumette B., Cichon S., Corvin A., Craddock N., Craig D., Degenhardt F., Djurovic S., Edenberg H.J., Fanous A.H., Foo J.C., Forstner A.J., Frye M., Fullerton J.M., Gatt J.M., Gejman P.V., Giegling I., Grabe H.J., Green M.J., Grevet E.H., Grigoroiu-Serbanescu M., Gutierrez B., Guzman-Parra J., Hamilton S.P., Hamshere M.L., Hartmann A., Hauser J., Heilmann-Heimbach S., Hoffmann P., Ising M., Jones I., Jones L.A., Jonsson L., Kahn R.S., Kelsoe J.R., Kendler K.S., Kloiber S., Koenen K.C., Kogevinas M., Konte B., Krebs M.-O., Landen M., Lawrence J., Leboyer M., Lee P.H., Levinson D.F., Liao C., Lissowska J., Lucae S., Mayoral F., McElroy S.L., McGrath P., McGuffin P., McQuillin A., Medland S.E., Mehta D., Melle I., Milaneschi Y., Mitchell P.B., Molina E., Morken G., Mortensen P.B., Muller-Myhsok B., Nievergelt C., Nimgaonkar V., Nothen M.M., O'Donovan M.C., Ophoff R.A., Owen M.J., Pato C., Pato M.T., Penninx B.W.J.H., Pimm J., Pistis G., Potash J.B., Power R.A., Preisig M., Quested D., Ramos-Quiroga J.A., Reif A., Ribases M., Richarte V., Rietschel M., Rivera M., Roberts A., Roberts G., Rouleau G.A., Rovaris D.L., Rujescu D., Sanchez-Mora C., Sanders A.R., Schofield P.R., Schulze T.G., Scott L.J., Serretti A., Shi J., Shyn S.I., Sirignano L., Sklar P., Smeland O.B., Smoller J.W., Sonuga-Barke E.J.S., Spalletta G., Strauss J.S., Swiatkowska B., Trzaskowski M., Turecki G., Vilar-Ribo L., Vincent J.B., Volzke H., Walters J.T.R., Shannon Weickert C., Weickert T.W., Weissman M.M., Williams L.M., Wray N.R., Zai C.C., Ashley-Koch A.E., Beckham J.C., Hauser E.R., Hauser M.A., Kimbrel N.A., Lindquist J.H., McMahon B., Oslin D.W., Qin X., Mattheisen M., Abdellaoui A., Adams M.J., Agerbo E., Andlauer T.F.M., Bacanu S.-A., Baekvad-Hansen M., Beekman A.T.F., Bryois J., Buttenschon H.N., Bybjerg-Grauholm J., Cai N., Christensen J.H., Clarke T.-K., Colodro-Conde L., Couvy-Duchesne B., Crawford G.E., Davies G., Derks E.M., Direk N., Dolan C.V., Dunn E.C., Eley T.C., Escott-Price V., Hassan Kiadeh F.F., Finucane H.K., Frank J., Gaspar H.A., Gill M., Goes F.S., Gordon S.D., Weinsheimer S.M., Wellmann J., Willemsen G., Wu Y., Xi H.S., Yang J., Zhang F., Arolt V., Boomsma D.I., Dannlowski U., de Geus E.J.C., Depaulo J.R., Domenici E., Domschke K., Esko T., Grove J., Hall L.S., Hansen C.S., Hansen T.F., Herms S., Hickie I.B., Homuth G., Horn C., Hottenga J.-J., Hougaard D.M., Howard D.M., Jansen R., Jorgenson E., Knowles J.A., Kohane I.S., Kraft J., Kretzschmar W.W., Kutalik Z., Li Y., Lind P.A., MacIntyre D.J., MacKinnon D.F., Maier R.M., Maier W., Marchini J., Mbarek H., Middeldorp C.M., Mihailov E., Milani L., Mondimore F.M., Montgomery G.W., Mostafavi S., Nauck M., Ng B., Nivard M.G., Nyholt D.R., O'Reilly P.F., Oskarsson H., Hayward C., Heath A.C., Lewis G., Li Q.S., Madden P.A.F., Magnusson P.K., Martin N.G., McIntosh A.M., Metspalu A., Mors O., Nordentoft M., Paciga S.A., Pedersen N.L., Painter J.N., Pedersen C.B., Pedersen M.G., Peterson R.E., Peyrot W.J., Posthuma D., Quiroz J.A., Qvist P., Rice J.P., Riley B.P., Mirza S.S., Schoevers R., Schulte E.C., Shen L., Sigurdsson E., Sinnamon G.C.B., Smit J.H., Smith D.J., Stefansson H., Steinberg S., Streit F., Strohmaier J., Tansey K.E., Teismann H., Teumer A., Thompson W., Thomson P.A., Thorgeirsson T.E., Traylor M., Treutlein J., Trubetskoy V., Uitterlinden A.G., Umbricht D., der Auwera S.V., van Hemert A.M., Viktorin A., Visscher P.M., Wang Y., Webb B.T., Perlis R.H., Porteous D.J., Schaefer C., Stefansson K., Tiemeier H., Uher R., Werge T., Lewis C.M., Breen G., Borglum A.D., Sullivan P.F., O'Connell K.S., Coombes B., Qiao Z., Als T.D., Borte S., Charney A.W., Drange O.K., Gandal M.J., Hagenaars S.P., Ikeda M., Kamitaki N., Krebs K., Panagiotaropoulou G., Schilder B.M., Sloofman L.G., Winsvold B.S., Won H.-H., Abramova L., Adorjan K., Al Eissa M., Albani D., Alliey-Rodriguez N., Antilla V., Antoniou A., Baek J.H., Bauer M., Beins E.C., Bergen S.E., Birner A., Boen E., Brum M., Brumpton B.M., Brunkhorst-Kanaan N., Byerley W., Cairns M., Cervantes P., Cruceanu C., Cuellar-Barboza A., Cunningham J., Curtis D., Czerski P.M., Dale A.M., Dalkner N., David F.S., Dobbyn A.L., Douzenis A., Elvsashagen T., Ferrier I.N., Fiorentino A., Foroud T.M., Forty L., Frei O., Freimer N.B., Frisen L., Gade K., Garnham J., Gelernter J., Gizer I.R., Gordon-Smith K., Greenwood T.A., Ha K., Haraldsson M., Hautzinger M., Heilbronner U., Hellgren D., Holmans P.A., Huckins L., Johnson J.S., Kalman J.L., Kamatani Y., Kittel-Schneider S., Koromina M., Kranz T.M., Kranzler H.R., Kubo M., Kupka R., Kushner S.A., Lavebratt C., Leber M., Lee H.-J., Levy S.E., Lewis C., Lundberg M., Magnusson S.H., Maihofer A., Malaspina D., Maratou E., Martinsson L., McGregor N.W., McKay J.D., Medeiros H., Millischer V., Moran J.L., Morris D.W., Muhleisen T.W., O'Brien N., O'Donovan C., Olde Loohuis L.M., Oruc L., Papiol S., Pardinas A.F., Perry A., Pfennig A., Porichi E., Raj T., Rapaport M.H., Regeer E.J., Rivas F., Roth J., Roussos P., Ruderfer D.M., Senner F., Sharp S., Shilling P.D., Slaney C., Sobell J.L., Artigas M.S., Spijker A.T., Stein D.J., Terao C., Toma C., Tooney P., Tsermpini E.-E., Vawter M.P., Vedder H., Xi S., Xu W., Kay Yang J.M., Young A.H., Young H., Zandi P.P., Zhou H., HUNT All-In Psychiatry, Babadjanova G., Backlund L., Bengesser S., Blackwood D.H.R., Carr V.J., Catts S., Dikeos D., Etain B., Ferentinos P., Gawlik M., Gershon E.S., Henskens F., Hillert J., Hong K.S., Hultman C.M., Hveem K., Iwata N., Jablensky A.V., Kirov G., Lochner C., Loughland C., Mathews C.A., McMahon F.J., Michie P., Mowry B., Neale B.M., Nievergelt C.M., Oedegaard K.J., Olsson T., Pantelis C., Patrinos G.P., Reininghaus E.Z., Saito T., Schall U., Schalling M., Scott R.J., Weickert C.S., Stordal E., Vaaler A.E., Vieta E., Waldman I.D., Zwart J.-A., Nurnberger J.I., Stahl E.A., Di Florio A., Adan R.A.H., Ando T., Aschauer H., Baker J.H., Bencko V., Birgegard A., Boden J.M., Boehm I., Boni C., Perica V.B., Buehren K., Bulik C.M., Burghardt R., Carlberg L., Cassina M., Clementi M., Cone R.D., Courtet P., Crowley J.J., Danner U.N., Davis O.S.P., de Zwaan M., Dedoussis G., Degortes D., DeSocio J.E., Dick D.M., Dina C., Dmitrzak-Weglarz M., Martinez E.D., Duncan L.E., Egberts K., Mattingsdal M., McDevitt S., Meulenbelt I., Micali N., Mitchell J., Mitchell K., Monteleone P., Monteleone A.M., Munn-Chernoff M.A., Nacmias B., Navratilova M., Ntalla I., Olsen C.M., O'Toole J.K., Padyukov L., Palotie A., Pantel J., Papezova H., Parker R., Pearson J.F., Ehrlich S., Escaramis G., Espeseth T., Estivill X., Farmer A., Favaro A., Fischer K., Floyd J.A.B., Focker M., Foretova L., Forzan M., Franklin C.S., Gambaro G., Giuranna J., Giusti-Rodriquez P., Gonidakis F., Gordon S., Mayora M.G., Guillaume S., Hanscombe K.B., Hatzikotoulas K., Hebebrand J., Helder S.G., Henders A.K., Herpertz-Dahlmann B., Herzog W., Hinney A., Horwood L.J., Hubel C., Petersen L.V., Purves K.L., Raevuori A., Reichborn-Kjennerud T., Ricca V., Ripatti S., Ritschel F., Roberts M., Rybakowski F., Santonastaso P., Scherag A., Schmidt U., Schork N.J., Schosser A., Seitz J., Slachtova L., Slagboom P.E., Slof-Op 't Landt M.C.T., Slopien A., Soranzo N., Sorbi S., Southam L., Steen V.W., Huckins L.M., Hudson J.I., Imgart H., Inoko H., Janout V., Jordan J., Julia A., Kalsi G., Kaminska D., Kaprio J., Karhunen L., Karwautz A., Kas M.J.H., Kennedy M.A., Keski-Rahkonen A., Kiezebrink K., Kim Y.-R., Kirk K.M., Klareskog L., Knudsen G.P.S., Larsen J.T., Le Hellard S., Leppa V.M., Lichtenstein P., Lin B.D., Lundervold A., Luykx J., Maj M., Mannik K., Marsal S., Stuber G.D., Szatkiewicz J.P., Tachmazidou I., Tenconi E., Tortorella A., Tozzi F., Tsitsika A., Tyszkiewicz-Nwafor M., Tziouvas K., van Elburg A.A., van Furth E.F., Wade T.D., Wagner G., Walton E., Whiteman D.C., Wichmann H.E., Widen E., Yao S., Zeggini E., Zerwas S., Zipfel S., Jungkunz M., Dietl L., Schwarze C.E., Dahmen N., Schott B.H., Mobascher A., Crivelli S., Dennis M.F., Harvey P.D., Carter B.W., Huffman J.E., Jacobson D., Madduri R., Olsen M.K., Pestian J., Gaziano J.M., Muralidhar S., Ramoni R., Beckham J., Chang K.-M., O'Donnell C.J., Tsao P.S., Breeling J., Huang G., Romero J.P.C., Moser J., Whitbourne S.B., Brewer J.V., Aslan M., Connor T., Argyres D.P., Stephens B., Brophy M.T., Humphries D.E., Selva L.E., Do N., Shayan S., Cho K., Pyarajan S., Hauser E., Sun Y., Zhao H., Wilson P., McArdle R., Dellitalia L., Mattocks K., Harley J., Zablocki C.J., Whittle J., Jacono F., Gutierrez S., Gibson G., Hammer K., Kaminsky L., Villareal G., Kinlay S., Xu J., Hamner M., Mathew R., Bhushan S., Iruvanti P., Godschalk M., Ballas Z., Ivins D., Mastorides S., Moorman J., Gappy S., Klein J., Ratcliffe N., Florez H., Okusaga O., Murdoch M., Sriram P., Yeh S.S., Tandon N., Jhala D., Aguayo S., Cohen D., Sharma S., Liangpunsakul S., Oursler K.A., Whooley M., Ahuja S., Constans J., Meyer P., Greco J., Rauchman M., Servatius R., Gaddy M., Wallbom A., Morgan T., Stapley T., Sherman S., Ross G., Tsao P., Strollo P., Boyko E., Meyer L., Gupta S., Huq M., Fayad J., Hung A., Lichy J., Hurley R., Robey B., Striker R., Erlangsen A., Kessler R.C., Porteous D., Ursano R.J., Wasserman D., Coon H., Demontis D., Docherty A.R., Kuo P.-H., Mann J.J., Renteria M.E., Stein M.B., and Willour V.
Subjects: LD SCORE REGRESSION, Genome-wide association study, Suicide, Attempted, 3124 Neurology and psychiatry, 0302 clinical medicine, Risk Factors, Insomnia, Suicide attempt, GWAS, Suïcidi, Depression (differential diagnoses), Cause of death, Psychiatry, 0303 health sciences, Factors de risc en les malalties, Mental Disorders, Genetic Correlation, Genome-wide Association Study, Pleiotropy, Polygenicity, Suicide, Suicide Attempt, DEPRESSION, 3. Good health, Genetic correlation, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Depressive Disorder, Major, Mental illness, Cohort, SEX, medicine.symptom, Human, medicine.medical_specialty, Risk factors in diseases, BF, Locus (genetics), BEHAVIORS, Psykiatri, EVENTS, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, ddc:610, GENOME-WIDE ASSOCIATION, IDEATION, Socioeconomic status, METAANALYSIS, Biological Psychiatry, 030304 developmental biology, business.industry, Risk Factor, Genetic architecture, THOUGHTS, RC0321, business, Malalties mentals, 030217 neurology & neurosurgery
Abstract: Statistical analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu), which is supported by the Office of Research Infrastructure of the National Institutes of Health (Grant Nos. S10OD018522 and S10OD026880). This work was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN. This work was funded by the National Institutes of Health (Grant Nos. R01MH116269 and R01MH121455 [to DMR]), NIGMS of the National Institutes of Health (Grant No. T32GM007347 [to JK]), and the Brain & Behavior Research Foundation (NARSAD Young Investigator Award No. 29551 [to NM])., BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders., Office of Research Infrastructure of the National Institutes of Health S10OD018522 S10OD026880, United States Department of Health & Human Services, National Institutes of Health (NIH) - USA R01MH116269 R01MH121455, NIH National Institute of General Medical Sciences (NIGMS) T32GM007347 NARSAD 29551
Published: 2022
Full Text: View/download PDF

83. Twin Family Registries Worldwide: An Important Resource for Scientific Research

Author: Catherine Tuvblad, Eivind Ystrom, Jeanette Taylor, Gonneke Willemsen, Juan R. Ordoñana, Christine Dalgård, Yoon-Mi Hur, Axel Skytthe, Sara A. Hart, and Leonie H. Bogl
Subjects: 0301 basic medicine, Economic growth, Biomedical Research, Project commissioning, MEDLINE, Globe, 030105 genetics & heredity, Article, 03 medical and health sciences, SDG 17 - Partnerships for the Goals, zygosity assessment, Resource (project management), Diseases in Twins, Twins, Dizygotic, Humans, Medicine, genetics, Registries, Genetics (clinical), twin family registry, recruitment of twins, business.industry, Obstetrics and Gynecology, Twins, Monozygotic, Twin Studies as Topic, Twin study, Audience measurement, 030104 developmental biology, medicine.anatomical_structure, multiple birth, Publishing, Pediatrics, Perinatology and Child Health, business, environment
Abstract: Much progress has been made in twin research since our last special issue on twin registries (Hur, Y.-M., & Craig, J. M. (2013). Twin Research and Human Genetics, 16, 1–12.). This special issue provides an update on the state of twin family registries around the world. This issue includes 61 papers on twin family registries from 25 countries, of which 3 describe consortia based on collaborations of several twin family registries. The articles included in this issue discuss the establishment and maintenance of twin registries, recruitment strategies, methods of zygosity assessment, research aims and major findings from twin family cohorts, as well as other important topics related to twin studies. The papers amount to approximately 1.3 million monozygotic, dizygotic twins and higher order multiples and their family members who participate in twin studies around the world. Nine new twin family registries have been established across the world since our last issue, which demonstrates that twin registers are increasingly important in studies of the determinants and correlates of complex traits from disease susceptibility to healthy development.
Published: 2019
Full Text: View/download PDF

84. Methylome-wide association study of antidepressant use in Generation Scotland and the Netherlands Twin Register implicates the innate immune system

Author: Miruna C. Barbu, Floris Huider, Archie Campbell, Carmen Amador, Mark J. Adams, Mary-Ellen Lynall, David M. Howard, Rosie M. Walker, Stewart W. Morris, Jenny Van Dongen, David J. Porteous, Kathryn L. Evans, Edward Bullmore, Gonneke Willemsen, Dorret I. Boomsma, Heather C. Whalley, Andrew M. McIntosh, Barbu, Miruna C [0000-0001-8967-683X], Campbell, Archie [0000-0003-0198-5078], Adams, Mark J [0000-0002-3599-6018], Lynall, Mary-Ellen [0000-0002-1939-7525], Howard, David M [0000-0002-6005-1972], Walker, Rosie M [0000-0002-1060-4479], Porteous, David J [0000-0003-1249-6106], Boomsma, Dorret I [0000-0002-7099-7972], Whalley, Heather C [0000-0002-4505-8869], McIntosh, Andrew M [0000-0002-0198-4588], Apollo - University of Cambridge Repository, Biological Psychology, APH - Personalized Medicine, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, APH - Methodology, and Bullmore, Edward [0000-0002-8955-8283]
Subjects: Depressive Disorder, Major, DNA methylation, major depressive disorder, innate immune system, methylome-wide association study, methylation-based score, antidepressant use, Pregnancy Proteins, Antidepressive Agents, Cellular and Molecular Neuroscience, Psychiatry and Mental health, Epigenome, Heme-Binding Proteins, Scotland, SDG 3 - Good Health and Well-being, Immune System, Humans, Molecular Biology, Netherlands
Abstract: Antidepressants are an effective treatment for major depressive disorder (MDD), although individual response is unpredictable and highly variable. Whilst the mode of action of antidepressants is incompletely understood, many medications are associated with changes in DNA methylation in genes that are plausibly linked to their mechanisms. Studies of DNA methylation may therefore reveal the biological processes underpinning the efficacy and side effects of antidepressants. We performed a methylome-wide association study (MWAS) of self-reported antidepressant use accounting for lifestyle factors and MDD in Generation Scotland (GS:SFHS, N = 6428, EPIC array) and the Netherlands Twin Register (NTR, N = 2449, 450 K array) and ran a meta-analysis of antidepressant use across these two cohorts. We found ten CpG sites significantly associated with self-reported antidepressant use in GS:SFHS, with the top CpG located within a gene previously associated with mental health disorders, ATP6V1B2 (β = -0.055, pcorrected = 0.005). Other top loci were annotated to genes including CASP10, TMBIM1, MAPKAPK3, and HEBP2, which have previously been implicated in the innate immune response. Next, using penalised regression, we trained a methylation-based score of self-reported antidepressant use in a subset of 3799 GS:SFHS individuals that predicted antidepressant use in a second subset of GS:SFHS (N = 3360, β = 0.377, p = 3.12 × 10-11, R2 = 2.12%). In an MWAS analysis of prescribed selective serotonin reuptake inhibitors, we showed convergent findings with those based on self-report. In NTR, we did not find any CpGs significantly associated with antidepressant use. The meta-analysis identified the two CpGs of the ten above that were common to the two arrays used as being significantly associated with antidepressant use, although the effect was in the opposite direction for one of them. Antidepressants were associated with epigenetic alterations in loci previously associated with mental health disorders and the innate immune system. These changes predicted self-reported antidepressant use in a subset of GS:SFHS and identified processes that may be relevant to our mechanistic understanding of clinically relevant antidepressant drug actions and side effects., NIHR Senior Investigator Award
Published: 2021
Full Text: View/download PDF

85. Plasma P‐tau181 levels predict amyloid pathology in cognitively unimpaired individuals after 10 years

Author: Anouk den Braber, Inge M.W. Verberk, Ben Den Dulk, Jori Tomassen, Jeffrey L Dage, Erik Stoops, Gonneke Willemsen, Michel G. Nivard, Bart N.M. Van Berckel, Philip Scheltens, Pieter Jelle Visser, Eco J.C. de Geus, and Charlotte E. Teunissen
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published: 2021
Full Text: View/download PDF

86. Investigating the relationships between unfavourable habitual sleep and metabolomic traits: evidence from multi-cohort multivariable regression and Mendelian randomization analyses

Author: Robert A. Schoevers, Mohsen Ghanbari, Annemarie I. Luik, Bastiaan T. Heijmans, Nienke R. Biermasz, Brenda W.J.H. Penninx, Carisha S. Thesing, Aeilko H. Zwinderman, Ruifang Li-Gao, Kaitlin H Wade, Frits R. Rosendaal, Dorret I. Boomsma, M. Arfan Ikram, Marian Beekman, Dennis O. Mook-Kanamori, Lisanne S. Vijfhuizen, P. Eline Slagboom, Debbie A Lawlor, Matthew Lee, Naveed Sattar, Matt J. Neville, Stella Trompet, J. Wouter Jukema, L.H. Lumey, Diana van Heemst, Ian Ford, Renée de Mutsert, Rima Mustafa, Patrick C.N. Rensen, Xiang Zhang, M.M. Bos, Abbas Dehghan, Carolien A. Wijsman, Gonneke Willemsen, Gisela M. Terwindt, Irene de Boer, Raymond Noordam, Ko Willems van Dijk, René Pool, Fredrik Karpe, Arn M. J. M. van den Maagdenberg, Neil Goulding, Rebecca C Richmond, Simon P. Mooijaart, Amy Hofman, Constantinos Christodoulides, Chihua Li, Mariska Bot, Neurosurgery, ANS - Neurodegeneration, ANS - Systems & Network Neuroscience, Epidemiology and Data Science, APH - Methodology, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Epidemiology, Biological Psychology, APH - Health Behaviors & Chronic Diseases, and APH - Personalized Medicine
Subjects: medicine.medical_specialty, Epidemiology, lcsh:Medicine, Physiology, Coronary Artery Disease, Polymorphism, Single Nucleotide, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Metabolic Diseases, SDG 3 - Good Health and Well-being, Risk Factors, Mendelian randomization, medicine, Insomnia, Humans, Metabolomics, Isoleucine, sleep, Aged, 030304 developmental biology, 2. Zero hunger, 0303 health sciences, Creatinine, business.industry, lcsh:R, Chronotype, General Medicine, Mendelian Randomization Analysis, R1, Confidence interval, 3. Good health, Cross-Sectional Studies, Phenotype, chemistry, Human and Animal Physiology, Cohort, Fysiologie van Mens en Dier, medicine.symptom, business, Sleep, Body mass index, 030217 neurology & neurosurgery, Research Article, Genome-Wide Association Study
Abstract: Background Sleep traits are associated with cardiometabolic disease risk, with evidence from Mendelian randomization (MR) suggesting that insomnia symptoms and shorter sleep duration increase coronary artery disease risk. We combined adjusted multivariable regression (AMV) and MR analyses of phenotypes of unfavourable sleep on 113 metabolomic traits to investigate possible biochemical mechanisms linking sleep to cardiovascular disease. Methods We used AMV (N = 17,368) combined with two-sample MR (N = 38,618) to examine effects of self-reported insomnia symptoms, total habitual sleep duration, and chronotype on 113 metabolomic traits. The AMV analyses were conducted on data from 10 cohorts of mostly Europeans, adjusted for age, sex, and body mass index. For the MR analyses, we used summary results from published European-ancestry genome-wide association studies of self-reported sleep traits and of nuclear magnetic resonance (NMR) serum metabolites. We used the inverse-variance weighted (IVW) method and complemented this with sensitivity analyses to assess MR assumptions. Results We found consistent evidence from AMV and MR analyses for associations of usual vs. sometimes/rare/never insomnia symptoms with lower citrate (− 0.08 standard deviation (SD)[95% confidence interval (CI) − 0.12, − 0.03] in AMV and − 0.03SD [− 0.07, − 0.003] in MR), higher glycoprotein acetyls (0.08SD [95% CI 0.03, 0.12] in AMV and 0.06SD [0.03, 0.10) in MR]), lower total very large HDL particles (− 0.04SD [− 0.08, 0.00] in AMV and − 0.05SD [− 0.09, − 0.02] in MR), and lower phospholipids in very large HDL particles (− 0.04SD [− 0.08, 0.002] in AMV and − 0.05SD [− 0.08, − 0.02] in MR). Longer total sleep duration associated with higher creatinine concentrations using both methods (0.02SD per 1 h [0.01, 0.03] in AMV and 0.15SD [0.02, 0.29] in MR) and with isoleucine in MR analyses (0.22SD [0.08, 0.35]). No consistent evidence was observed for effects of chronotype on metabolomic measures. Conclusions Whilst our results suggested that unfavourable sleep traits may not cause widespread metabolic disruption, some notable effects were observed. The evidence for possible effects of insomnia symptoms on glycoprotein acetyls and citrate and longer total sleep duration on creatinine and isoleucine might explain some of the effects, found in MR analyses of these sleep traits on coronary heart disease, which warrant further investigation.
Published: 2021
Full Text: View/download PDF

87. Identical twins carry a persistent epigenetic signature of early genome programming

Author: Jordana T. Bell, Claudio D. Stern, Scott D. Gordon, Erik A. Ehli, Silvère M. van der Maarel, Jonathan Mill, Gibran Hemani, Hamdi Mbarek, Juan E. Castillo-Fernandez, Tim D. Spector, Allan F. McRae, Catharina E. M. van Beijsterveldt, Jouke-Jan Hottenga, Veronika V. Odintsova, Nicholas G. Martin, Jaakko Kaprio, Eilis Hannon, P. Eline Slagboom, Gonneke Willemsen, Bastiaan T. Heijmans, Sara N. Lundgren, Josine L. Min, Jenny van Dongen, Miina Ollikainen, Dorret I. Boomsma, Pei-Chien Tsai, Karen Sugden, Charles E. Breeze, Terrie E. Moffitt, Bruno Reversade, Lucia Daxinger, Franziska Paul, Fiona A. Hagenbeek, Eco J. C. de Geus, Grant W. Montgomery, T.D. Spector, Avshalom Caspi, Center for Reproductive Medicine, ACS - Heart failure & arrhythmias, Amsterdam Reproduction & Development, Reversade, Bruno, van Dongen, Jenny, Gordon, Scott D., McRae, Allan F., Odintsova, Veronika V., Mbarek, Hamdi, Breeze, Charles E., Sugden, Karen, Lundgren, Sara, Castillo-Fernandez, Juan E., Hannon, Eilis, Moffitt, Terrie E., Hagenbeek, Fiona A., van Beijsterveldt, Catharina E. M., Hottenga, Jouke Jan, Tsai, Pei-Chien, Min, Josine L., Hemani, Gibran, Ehli, Erik A., Paul, Franziska, Stern, Claudio D., Heijmans, Bastiaan T., Slagboom, P. Eline, Daxinger, Lucia, van der Maarel, Silvere M., de Geus, E. J. C., Willemsen, Gonneke, Montgomery, Grant W., Ollikainen, Miina, Kaprio, Jaakko, Spector, Tim D., Bell, Jordana T., Mill, Jonathan, Caspi, Avshalom, Martin, Nicholas G., Boomsma, Dorret, I., School of Medicine, APH - Personalized Medicine, APH - Mental Health, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Methodology, Breeze, Charles, Martin, Nicholas, Boomsma, Dorret, Institute for Molecular Medicine Finland, and Epigenetics of Complex Diseases and Traits
Subjects: Epigenomics, Somatic cell, General Physics and Astronomy, Monozygotic twin, PROBE DESIGN BIAS, Genome, Epigenesis, Genetic, NORMALIZATION, 0302 clinical medicine, Genetics research, Registries, Probe design bias, DNA methylation, Vanishing twin, Register, Cells, Normalization, Association, Ontology, Mothers, Family, 112 Statistics and probability, Science and technology, Finland, Netherlands, 0303 health sciences, Multidisciplinary, Zygote, Twinning, Monozygotic, MOTHERS, 1184 Genetics, developmental biology, physiology, VANISHING TWIN, ASSOCIATION, Middle Aged, 3142 Public health care science, environmental and occupational health, FAMILY, Multidisciplinary sciences, Embryogenesis, Adult, Genotype, Heterochromatin, Science, Quantitative Trait Loci, Biology, Polymorphism, Single Nucleotide, Article, General Biochemistry, Genetics and Molecular Biology, Young Adult, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Centromere, Humans, Epigenetics, Genetic epigenesis, REGISTER, Retrospective Studies, 030304 developmental biology, 3112 Neurosciences, Twins, Monozygotic, General Chemistry, United Kingdom, 3141 Health care science, ONTOLOGY, Evolutionary biology, CELLS, 030217 neurology & neurosurgery
Abstract: The mechanisms underlying how monozygotic (or identical) twins arise are yet to be determined. Here, the authors investigate this in an epigenome-wide association study, showing that monozygotic twinning has a characteristic DNA methylation signature in adult somatic tissues. Monozygotic (MZ) twins and higher-order multiples arise when a zygote splits during pre-implantation stages of development. The mechanisms underpinning this event have remained a mystery. Because MZ twinning rarely runs in families, the leading hypothesis is that it occurs at random. Here, we show that MZ twinning is strongly associated with a stable DNA methylation signature in adult somatic tissues. This signature spans regions near telomeres and centromeres, Polycomb-repressed regions and heterochromatin, genes involved in cell-adhesion, WNT signaling, cell fate, and putative human metastable epialleles. Our study also demonstrates a never-anticipated corollary: because identical twins keep a lifelong molecular signature, we can retrospectively diagnose if a person was conceived as monozygotic twin., Netherlands Organization for Scientific Research (NWO); Biobanking and Biomolecular Research Infrastructure (BBMRI–NL); NWO Large Scale infrastructures; X-Omics
Published: 2021
Full Text: View/download PDF

88. Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability

Author: Tove Fall, Anubha Mahajan, Dmitry Shungin, B. Balkau, Gerjan Navis, A. Metspalu, Anneli Pouta, Andrew A. Hicks, Ilja M. Nolte, Ian Ford, Aroon D. Hingorani, Stefan R Bornstein, Anuj Goel, Rona J. Strawbridge, Niek Verweij, Sarah H. Wild, Patricia B. Munroe, T.B. Harris, Jaana Lindström, Johnson Pcd., Nita G. Forouhi, Pierre Meneton, Patricia A. Peyser, Sarin A-P., Andrea Ganna, Timothy M. Frayling, Patrik K. E. Magnusson, Joanne M. Meyer, Yongmei Liu, Jeanette M. Stafford, Christian Herder, L Zudina, Maria G. Stathopoulou, May E. Montasser, Nicholas D. Hastie, Inês Barroso, Schwarz Peh., James B. Meigs, Perttu Salo, George Davey Smith, Gonneke Willemsen, Christopher J. Groves, Erik P A Van Iperen, M. A. Province, Veikko Salomaa, Naveed Sattar, Serena Sanna, Maria Dimitriou, Joop Jukema, Ulrika Krus, Albert V. Smith, Markku Laakso, James F. Wilson, George Nicholson, Loic Yengo, Tatijana Zemunik, Per Eriksson, Harold Snieder, Peter P. Pramstaller, Claudia Langenberg, R. Rauramaa, Alan R. Shuldiner, Pau Navarro, Veronique Vitart, Ross M. Fraser, Aaron Isaacs, C. Lecoeur, Jesper R. Gådin, Jackie F. Price, Letizia Marullo, L.F. Bielak, Sirkka Keinänen-Kiukaanniemi, Amélie Bonnefond, Michael Stumvoll, Alessia Faggian, Anke Tönjes, Tomohiro Tanaka, Wieland Kiess, Harry Campbell, Josée Dupuis, David Altshuler, João Fadista, Winfried März, G K Hovingh, Thomas Illig, Toby Johnson, H Grallert, Kari Stefansson, Reedik Mägi, Palmer Cna., de Geus Ejcn., Martina Müller-Nurasyid, Karen Kapur, Philippe Froguel, Dorret I. Boomsma, Anders Franco-Cereceda, Marcus E. Kleber, Boehnke M, Olga D. Carlson, Ozren Polasek, Andrew P. Morris, Alex S. F. Doney, Najaf Amin, Sara M. Willems, Vilmundur Gudnason, Jose C. Florez, Jeffery R. O'Connell, Nancy L. Pedersen, T. Saaristo, Wolffenbuttel Bhr., M. I. J. Uusitupa, Longda Jiang, Iva Miljkovic, James S. Pankow, Caroline Hayward, Hugh Watkins, Vasiliki Lagou, Johanna Kuusisto, Jaakko Tuomilehto, Alan F. Wright, Josephine M. Egan, Perry Jrb., C M van Duijn, Valeriya Lyssenko, Leif Groop, Stefania Bandinelli, Nigel W. Rayner, Tõnu Esko, Stela McLachlan, Momoko Horikoshi, Eric Boerwinkle, Rick Jansen, Richard N. Bergman, Gudmar Thorleifsson, Lyle J. Palmer, Vilmantas Giedraitis, Peter Kovacs, Nicholas J. Wareham, Luigi Ferrucci, N J Timpson, D Rybin, Anne U. Jackson, Tiinamaija Tuomi, Gonçalo R. Abecasis, Harst Pvd., Meena Kumari, Albert Hofman, Chiara Scapoli, Evelin Mihailov, Josine L. Min, Anders Hamsten, Hottenga J-J., Loos Rjf., Lars Lind, Ulf de Faire, Jaakko Kaprio, Guo Li, Beate St Pourcain, C Gieger, Amanda J. Bennett, Anna Ulrich, Nabila Bouatia-Naji, Satu Männistö, Antigone S. Dimas, Jarvelin M-R., Günther Silbernagel, F Karpe, A. Körner, David S. Siscovick, M Blüher, Rebecca J. Webster, Erik Ingelsson, Susan Campbell, Mika Kivimäki, Laura J. Rasmussen-Torvik, Heikki A. Koistinen, Sophie Visvikis-Siest, Bernhard O. Boehm, Inga Prokopenko, Ping An, Emmanouil T. Dermitzakis, Cecilia M. Lindgren, Kardia Slr., Richa Saxena, Igor Rudan, Richard M. Watanabe, Jian'an Luan, Marika Kaakinen, Shin S-Y., George Dedoussis, Panagiotis Deloukas, Mark I. McCarthy, Barbara Thorand, B.W.J.H. Penninx, Peter Vollenweider, Paul W. Franks, Leena Kinnunen, Markus Perola, Yvonne Boettcher, Timo A. Lakka, Nicole Soranzo, Stavroula Kanoni, Bakker Sjl., Winkelmann Br, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Institute of Genomics [Tartu, Estonia], University of Tartu, Vrije Universiteit Amsterdam [Amsterdam] (VU), Vrije Universiteit Medical Centre (VUMC), Helmholtz-Zentrum München (HZM), University of Cambridge [UK] (CAM), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Università degli Studi di Ferrara (UniFE), Boston University [Boston] (BU), VU University Medical Center [Amsterdam], University of Bristol [Bristol], Biomedical Sciences Research Centre Alexander Fleming [Vari, Greece] (BSRC), Imperial College London, Karolinska Institutet [Stockholm], Institute for Molecular Bioscience, University of Queensland [Brisbane], Statens Serum Institut [Copenhagen], Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Cardiovascular Research Institute Maastricht (CARIM), Maastricht University [Maastricht], MRC Institute of Genetics and Molecular Medicine [Edinburgh] (IGMM), University of Edinburgh-Medical Research Council, National Institute on Aging [Baltimore, MD, USA] (NIH), University of Michigan [Ann Arbor], University of Michigan System, University of Maryland School of Medicine, University of Maryland System, The University of Western Australia (UWA), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Wake Forest University, National Institute for Health and Welfare [Helsinki], The Wellcome Trust Sanger Institute [Cambridge], University of Iceland [Reykjavik], University of Washington [Seattle], University of Groningen [Groningen], University of Glasgow, William Harvey Research Institute, Barts and the London Medical School, Université de Lausanne (UNIL), deCODE genetics [Reykjavik], Northwestern University Feinberg School of Medicine, Uppsala Universitet [Uppsala], University of Edinburgh, Medical Faculty [Mannheim], University of Graz, Ludwig-Maximilians-Universität München (LMU), Johannes Gutenberg - Universität Mainz (JGU), Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki-University of Helsinki, Umeå University, Skane University Hospital [Malmo], Lund University [Lund], RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche [Roma] (CNR), University Medical Center Groningen [Groningen] (UMCG), Universität Leipzig [Leipzig], Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Split, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), University of Eastern Finland, Harokopio University of Athens, European Academy Bozen/Bolzano (EURAC), University of Kuopio, German Center for Diabetes Research - Deutsches Zentrum für Diabetesforschung [Neuherberg] (DZD), University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Ninewells Hospital and Medical School [Dundee], University College of London [London] (UCL), University of Essex, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], University of Helsinki, Leiden University Medical Center (LUMC), Institute of Cardiovascular and Medical Sciences [Glasgow], University of Oulu, The University of Texas Health Science Center at Houston (UTHealth), University of Minnesota Medical School, University of Minnesota System, Keck School of Medicine [Los Angeles], University of Southern California (USC), Amsterdam UMC, University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Lee Kong Chian School of Medicine, Nanyang Technological University (NTU), Universität Heidelberg [Heidelberg], King Abdulaziz University, Pirkanmaa Hospital District, Tampere University Hospital, Cedars-Sinai Medical Center, Danube University Krems, Harvard School of Public Health, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institute of Epidemiology [Neuherberg] (EPI), German Research Center for Environmental Health - Helmholtz Center München (GmbH), Hannover Medical School [Hannover] (MHH), Universität zu Lübeck [Lübeck], University of Exeter, Regeneron Pharmaceuticals [Tarrytown], University of Adelaide, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Harvard T.H. Chan School of Public Health, John Radcliffe Hospital [Oxford University Hospital], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Université de Genève (UNIGE), Big Data Institute, University of Surrey (UNIS), University of Bergen (UiB), Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Stanford Cardiovascular Institute, University of Liverpool, University of Manchester [Manchester], Institute of Biochemistry and Genetics of Ufa Scientific Centre, Russian Academy of Sciences [Moscow] (RAS), Experimental Vascular Medicine, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, SIEST, Sofia, PreciDIAB Institute, the holistic approach of personal diabets care - - PreciDIAB2018 - ANR-18-IBHU-0001 - IBHU - VALID, Understanding the dynamic determinants of glucose homeostasis and social capability to promote Healthy and active aging - DYNAHEALTH - - H20202015-04-01 - 2019-03-31 - 633595 - VALID, Beyond the Genetics of Addiction - ADDICTION - - EC:FP7:ERC2011-12-01 - 2017-05-31 - 284167 - VALID, Rise of scientific excellence and collaboration for implementing personalised medicine in Estonia - ePerMed - - H20202016-01-01 - 2018-12-31 - 692145 - VALID, University of Oxford, Helmholtz Zentrum München = German Research Center for Environmental Health, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Università degli Studi di Ferrara = University of Ferrara (UniFE), Université de Lausanne = University of Lausanne (UNIL), Karl-Franzens-Universität Graz, Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Amsterdam UMC - Amsterdam University Medical Center, Nanyang Technological University [Singapour], Universität zu Lübeck = University of Lübeck [Lübeck], Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, Université de Genève = University of Geneva (UNIGE), ANR-18-IBHU-0001,PreciDIAB,PreciDIAB Institute, the holistic approach of personal diabets care(2018), European Project: 633595,H2020,H2020-PHC-2014-two-stage,DYNAHEALTH(2015), European Project: 284167,EC:FP7:ERC,ERC-2011-StG_20101124,ADDICTION(2011), European Project: 692145,H2020,H2020-TWINN-2015,ePerMed(2016), Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Functional Genomics, APH - Mental Health, Sociology and Social Gerontology, APH - Methodology, Hottenga, Jouke- Jan [0000-0002-5668-2368], Bouatia-Naji, Nabila [0000-0001-5424-2134], Jansen, Rick [0000-0002-3333-6737], Min, Josine L. [0000-0003-4456-9824], Faggian, Alessia [0000-0002-3799-9722], Bonnefond, Amélie [0000-0001-9976-3005], Isaacs, Aaron [0000-0001-5037-4834], Willems, Sara M. [0000-0002-6803-3007], Navarro, Pau [0000-0001-5576-8584], Jackson, Anne U. [0000-0002-9672-2547], Bielak, Lawrence F. [0000-0002-3443-8030], Saxena, Richa [0000-0003-2233-1065], Smith, Albert V. [0000-0003-1942-5845], Verweij, Niek [0000-0002-4303-7685], Goel, Anuj [0000-0003-2307-4021], Johnson, Paul C. D. [0000-0001-6663-7520], Strawbridge, Rona J. [0000-0001-8506-3585], Fall, Tove [0000-0003-2071-5866], Fraser, Ross M. [0000-0003-0488-2592], Kanoni, Stavroula [0000-0002-1691-9615], Giedraitis, Vilmantas [0000-0003-3423-2021], Kleber, Marcus E. [0000-0003-0663-7275], Müller-Nurasyid, Martina [0000-0003-3793-5910], Luan, Jian’an [0000-0003-3137-6337], Sanna, Serena [0000-0002-3768-1749], Nolte, Ilja M. [0000-0001-5047-4077], Zemunik, Tatijana [0000-0001-8120-2891], Kovacs, Peter [0000-0002-0290-5423], Wild, Sarah H. [0000-0001-7824-2569], McLachlan, Stela [0000-0003-0480-6143], Egan, Josephine [0000-0002-8945-0053], Hicks, Andrew A. [0000-0001-6320-0411], Thorand, Barbara [0000-0002-8416-6440], Hingorani, Aroon [0000-0001-8365-0081], Kivimaki, Mika [0000-0002-4699-5627], Koistinen, Heikki A. [0000-0001-7870-070X], Bakker, Stephan J. L. [0000-0003-3356-6791], Palmer, Colin N. A. [0000-0002-6415-6560], Jukema, J. Wouter [0000-0002-3246-8359], Sattar, Naveed [0000-0002-1604-2593], Snieder, Harold [0000-0003-1949-2298], Magnusson, Patrik K. [0000-0002-7315-7899], Blüher, Matthias [0000-0003-0208-2065], Wolffenbuttel, Bruce H. R. [0000-0001-9262-6921], Abecasis, Goncalo R. [0000-0003-1509-1825], Meigs, James B. [0000-0002-2439-2657], Wilson, James F. [0000-0001-5751-9178], Schwarz, Peter E. H. [0000-0001-6317-7880], Boehm, Bernhard O. [0000-0002-2706-7710], Metspalu, Andres [0000-0002-3718-796X], Deloukas, Panos [0000-0001-9251-070X], Körner, Antje [0000-0001-6001-0356], Wareham, Nicholas J. [0000-0003-1422-2993], Langenberg, Claudia [0000-0002-5017-7344], Männistö, Satu [0000-0002-8668-3046], Franks, Paul W. [0000-0002-0520-7604], Hayward, Caroline [0000-0002-9405-9550], Vitart, Veronique [0000-0002-4991-3797], Kaprio, Jaakko [0000-0002-3716-2455], Visvikis-Siest, Sophie [0000-0001-8104-8425], Altshuler, David [0000-0002-7250-4107], Rudan, Igor [0000-0001-6993-6884], van Duijn, Cornelia M. [0000-0002-2374-9204], Pramstaller, Peter P. [0000-0002-9831-8302], Boehnke, Michael [0000-0002-6442-7754], Frayling, Timothy M. [0000-0001-8362-2603], Peyser, Patricia A. [0000-0002-9717-8459], Harst, Pim van der [0000-0002-2713-686X], Smith, George Davey [0000-0002-1407-8314], Forouhi, Nita G. [0000-0002-5041-248X], Loos, Ruth J. F. [0000-0002-8532-5087], Salomaa, Veikko [0000-0001-7563-5324], Soranzo, Nicole [0000-0003-1095-3852], Boomsma, Dorret I. [0000-0002-7099-7972], Groop, Leif [0000-0002-0187-3263], Tuomi, Tiinamaija [0000-0002-8306-6202], Munroe, Patricia B. [0000-0002-4176-2947], Gudnason, Vilmundur [0000-0001-5696-0084], Lecoeur, Cecile [0000-0003-0075-6417], Jarvelin, Marjo-Riitta [0000-0002-2149-0630], Stefansson, Kari [0000-0003-1676-864X], Dermitzakis, Emmanouil T. [0000-0002-9302-6490], Lindgren, Cecilia M. [0000-0002-4903-9374], Froguel, Philippe [0000-0003-2972-0784], Kaakinen, Marika A. [0000-0002-9228-0462], Watanabe, Richard M. [0000-0003-1015-0531], Ingelsson, Erik [0000-0003-2256-6972], Dupuis, Josée [0000-0003-2871-3603], Barroso, Inês [0000-0001-5800-4520], Apollo - University of Cambridge Repository, Epidemiology, University Hospital Mannheim | Universitätsmedizin Mannheim, National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Universität Leipzig, Universiteit Leiden, Universität Heidelberg [Heidelberg] = Heidelberg University, Karl-Franzens-Universität [Graz, Autriche], Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, General practice, APH - Digital Health, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Lifestyle Medicine (LM), Groningen Institute for Organ Transplantation (GIOT), Groningen Kidney Center (GKC), Center for Liver, Digestive and Metabolic Diseases (CLDM), Value, Affordability and Sustainability (VALUE), Cardiovascular Centre (CVC), Hottenga, Jouke-Jan [0000-0002-5668-2368], Min, Josine L [0000-0003-4456-9824], Willems, Sara M [0000-0002-6803-3007], Jackson, Anne U [0000-0002-9672-2547], Bielak, Lawrence F [0000-0002-3443-8030], Smith, Albert V [0000-0003-1942-5845], Johnson, Paul CD [0000-0001-6663-7520], Strawbridge, Rona J [0000-0001-8506-3585], Fraser, Ross M [0000-0003-0488-2592], Kleber, Marcus E [0000-0003-0663-7275], Luan, Jian'an [0000-0003-3137-6337], Nolte, Ilja M [0000-0001-5047-4077], Wild, Sarah H [0000-0001-7824-2569], Hicks, Andrew A [0000-0001-6320-0411], Koistinen, Heikki A [0000-0001-7870-070X], Bakker, Stephan JL [0000-0003-3356-6791], Palmer, Colin NA [0000-0002-6415-6560], Jukema, J Wouter [0000-0002-3246-8359], Magnusson, Patrik K [0000-0002-7315-7899], Wolffenbuttel, Bruce HR [0000-0001-9262-6921], Abecasis, Goncalo R [0000-0003-1509-1825], Meigs, James B [0000-0002-2439-2657], Wilson, James F [0000-0001-5751-9178], Schwarz, Peter EH [0000-0001-6317-7880], Boehm, Bernhard O [0000-0002-2706-7710], Wareham, Nicholas J [0000-0003-1422-2993], Franks, Paul W [0000-0002-0520-7604], van Duijn, Cornelia M [0000-0002-2374-9204], Pramstaller, Peter P [0000-0002-9831-8302], Frayling, Timothy M [0000-0001-8362-2603], Peyser, Patricia A [0000-0002-9717-8459], Forouhi, Nita G [0000-0002-5041-248X], Loos, Ruth JF [0000-0002-8532-5087], Boomsma, Dorret I [0000-0002-7099-7972], Munroe, Patricia B [0000-0002-4176-2947], Dermitzakis, Emmanouil T [0000-0002-9302-6490], Lindgren, Cecilia M [0000-0002-4903-9374], Kaakinen, Marika A [0000-0002-9228-0462], Watanabe, Richard M [0000-0003-1015-0531], Tampere University, Tays Research Services, Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC), Fysiologie, RS: FHML MaCSBio, and RS: Carim - B01 Blood proteins & engineering
Subjects: Male, Anorexia Nervosa, medicine.medical_treatment, 45/43, Insulin Resistance/genetics, SUSCEPTIBILITY, Quantitative trait, Impaired glucose tolerance, 0302 clinical medicine, Architecture, LS2_1, IMPUTATION, Insulin, ComputingMilieux_MISCELLANEOUS, Fasting, Publisher Correction, 3. Good health, [SDV] Life Sciences [q-bio], Kruppel-Like Transcription Factors/blood, Endokrinologi och diabetes, Science & Technology - Other Topics, Adult, Blood Glucose, European Continental Ancestry Group, Female, Gene Expression, Genetic Loci, Genome-Wide Association Study, Glucose Intolerance, Humans, Insulin Receptor Substrate Proteins, Insulin Resistance, Kruppel-Like Transcription Factors, Middle Aged, Phenotype, Sex Characteristics, Sex Factors, Waist-Hip Ratio, Sex characteristics, medicine.medical_specialty, Science, 631/208/205/2138, Endocrinology and Diabetes, General Biochemistry, Genetics and Molecular Biology, White People, Gender-differences, 03 medical and health sciences, SDG 3 - Good Health and Well-being, 692/53/2421, GLYCEMIC TRAITS, GENOME-WIDE ASSOCIATION, Glycemic, GENDER-DIFFERENCES, Science & Technology, IDENTIFICATION, 692/699/2743/2815, Blood Glucose/metabolism, Diagnostic markers, medicine.disease, Anorexia Nervosa/blood, 030104 developmental biology, Endocrinology, Glucose, Insulin/blood, Anorexia Nervosa/ethnology, Anorexia Nervosa/genetics, Anorexia Nervosa/physiopathology, Fasting/blood, Glucose Intolerance/blood, Glucose Intolerance/ethnology, Glucose Intolerance/genetics, Glucose Intolerance/physiopathology, Insulin Receptor Substrate Proteins/blood, Insulin Receptor Substrate Proteins/genetics, Kruppel-Like Transcription Factors/genetics, 0301 basic medicine, Identification, [SDV]Life Sciences [q-bio], General Physics and Astronomy, Genome-wide association studies, Waist–hip ratio, LS4_5, RISK, ARCHITECTURE, Multidisciplinary, article, Type 2 diabetes, Multidisciplinary Sciences, MENDELIAN RANDOMIZATION, Pre-diabetes, Medical Genetics, Risk, PATHOPHYSIOLOGY, 030209 endocrinology & metabolism, 3121 Internal medicine, 692/163/2743/137/773, NO, Insulin resistance, Internal medicine, Diabetes mellitus, medicine, Mendelian randomization, 631/208/480, Medicinsk genetik, business.industry, General Chemistry, Impaired fasting glucose, business
Abstract: Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes., Sex differences in fasting glucose and insulin have been identified, but the genetic loci underlying these differences have not. Here, the authors perform a meta-analysis of genome-wide association studies to detect sex-specific and sex-dimorphic loci associated with fasting glucose and insulin.
Published: 2021
Full Text: View/download PDF

89. DNA methylation in peripheral tissues and Left-handedness

Author: Veronika Odintsova, Matthew Sudermann, Fiona Hagenbeek, Doretta Caramaschi, Jouke-Jan Hottenga, Rene Pool, Biobank-based Integrative Omics Study Consortium BIOS, Conor Dolan, Lannie Ligthart, Catharina van Beijsterveldt, Gonneke Willemsen, Eco de Geus, Jeffrey Beck, Erik Ehli, Gabriel Cuellar-Partida, David Evans, Sarah Medland, Caroline Relton, Dorret Boomsma, and Jenny van Dongen
Subjects: Pathology, medicine.medical_specialty, DNA methylation, medicine, Biology, Left handedness, Peripheral
Abstract: Handedness has low heritability and epigenetic mechanisms have been proposed as an etiological mechanism. To examine this hypothesis, we performed an epigenome-wide association study (EWAS) of left-handedness. In a meta-analysis of 3,914 adults of whole-blood DNA methylation, we observed that CpG sites located in proximity of handedness-associated genetic variants were more strongly associated with left-handedness than other CpG sites (P = 0.04), but did not identify any differentially methylated positions. We identified differentially methylated regions at 20q11.23 (P = 0.00004) and 2p25.1 (P = 0.03), which were less methylated in left-handed adults. In longitudinal analyses of DNA methylation in peripheral blood and buccal cells from children (N = 1,737), we observed moderately stable associations across age (correlation range [0.355–0.578]) but inconsistent across tissues (correlation range [-0.384-0.318]). We conclude that DNA methylation in peripheral tissues captures little of the variance in handedness. Future investigations should consider other more targeted sources of tissue, such as the brain.
Published: 2021
Full Text: View/download PDF

90. Genetic insights into biological mechanisms governing human ovarian ageing

Author: Unnur Styrkarsdottir, Lynda M. Rose, Rehannah Borup, Anne B. Newman, Georgia Chenevix-Trench, Chikashi Terao, Jeremy A. Daniel, Christa Meisinger, Albert V. Smith, Emil Peter Thrane Hertz, Raymond Noordam, Wei He, Jennifer A. Smith, Mikael Eriksson, Konstantin Strauch, Daniel I. Chasman, Nicholas J. Timpson, Melissa A. Troester, Claudia Langenberg, Montserrat Garcia-Closas, Mohammad Arfan Ikram, Sara Lindström, Gad Rennert, Pascal Guénel, Kristina W. Olsen, Pierre Fontanillas, Ozren Polasek, Daniel F. Gudbjartsson, Frank B. Hu, Archie Campbell, Celine M. Vachon, Sheila Ulivi, Robin N Beaumont, Robert Karlsson, Lenore J. Launer, Renée de Mutsert, Annette Peters, David Schlessinger, Stefania Bandinelli, Rico Rueedi, Joop S.E. Laven, Pascal Timshel, Joanne M. Murabito, Kuang Lin, Jazib Hussain, Dennis O. Mook-Kanamori, Manjeet K. Bolla, Catherine E. Aiken, Javier Martin Gonzalez, Simon S. Cross, Immaculata De Vivo, Paul M. Ridker, Christopher A. Haiman, Gerardo Heiss, Jessica Tyrrell, Paul R. H. J. Timmers, Hironori Abe, Mike A. Nalls, Luigi Ferrucci, Natalia Perjakova, Jouke J. Hottenga, Robin G. Walters, Reedik Mägi, Niclas Håkansson, Miriam Dwek, Barbara McKnight, Sandra Turon, Stasa Stankovic, Linda Broer, Stephen J. Chanock, Martina La Bianca, Jenny Chang-Claude, Loic Le Marchand, Hamdi Mbarek, Doris Stöckl, Andrew F. Olshan, Graham G. Giles, James F. Wilson, Micaella Joaquim, Amruta Shrikhande, Eva Hoffmann, Stefania Benonisdottir, Ana Martínez-Marchal, Anthony J. Swerdlow, David Karasik, Nicholas J. Wareham, Peter A. Fasching, Jane L. Tarry-Adkins, Charles Kooperberg, Peter Vollenweider, Douglas F. Easton, Paula Aguilera, Jessica D. Faul, Patrik K. E. Magnusson, Emmanouil Saloustros, Alpa V. Patel, Ellen W. Demerath, Qin Wang, Aditya Sankar, Christopher G. Scott, Iffat Rahman, Sharon L.R. Kardia, Peter K. Joshi, Caterina Barbieri, Claus Yding Andersen, Tõnu Esko, Massimo Mezzavilla, Nicholas G. Martin, Rebecca D. Jackson, Alison D. Murray, Marina Ciullo, Nicholas Bowker, Anna Murray, Patrick Deelen, Zoltán Kutalik, Alicja Wolk, Manuela Gago-Dominguez, Eleonora Porcu, Laura Crisponi, Michela Traglia, Katharina E. Schraut, Antonietta Robino, Chunyan He, Bruce H. R. Wolffenbuttel, Henry Völzke, Daniela Ruggiero, John R. B. Perry, Lude Franke, Igor Rudan, Angela Cox, Unnur Þorsteinsdottir, Christian Gieger, David R. Weir, Jodie N. Painter, Martha S. Linet, Massimo Mangino, Melissa C. Southey, Petr Solc, Tim D. Spector, Christiana Kartsonaki, Momoko Horikoshi, Meir J. Stampfer, Eulalia Catamo, Mònica Ferrer-Roda, Ko Willems van Dijk, Daniela Toniolo, Caroline Hayward, Lili Milani, Chloé Sarnowski, Jian'an Luan, Behrooz Z. Alizadeh, Jenny A. Visser, Stig E. Bojesen, Genevieve Lachance, Ulrike Peters, Antonella Mulas, John J. Spinelli, Elnaz Naderi, Andrew R. Wood, Paul D.P. Pharoah, Elinor J. Sawyer, Annique Claringbould, Saleh Shekari, David G. Hunter, Marie Louise Grøndahl, Vilmundur Gudnason, Nora Franceschini, Dale P. Sandler, Dale R. Nyholt, Jacques E. Rossouw, Amber N. Wilcox, Thomas U. Ahearn, Hedy S. Rennert, Olivier B. Bakker, Jingmei Li, Francesco Cucca, Eric Boerwinkle, Matthias W. Beckmann, Cristina Menni, Minouk J. Schoemaker, Esther M. John, Tune H. Pers, Andrés J. López-Contreras, Tanguy Corre, Jonathan Marten, Alice M. Arnold, N. Charlotte Onland-Moret, Lucie Knoblochova, Anna Pujol, Kathryn L. Lunetta, Marjanka K. Schmidt, Teresa Nutile, Serena Sanna, Gonneke Willemsen, Roger L. Milne, Kristan J. Aronson, Frits R. Rosendaal, Murielle Bochud, Ken K. Ong, Susan M. Ring, Nancy L. Pedersen, Blair H. Smith, Ivana Kolcic, Annelie Augustinsson, Jose E. Castelao, Alexander Teumer, Felix R. Day, Sven Bergmann, Timothy M. Frayling, Lauren R. Teras, George Davey Smith, Thomas Meitinger, Alison M. Dunning, Ignasi Roig, Dorret I. Boomsma, Harald Grallert, Toshiko Tanaka, Katherine S. Ruth, Julie E. Buring, Marek Zygmunt, Uwe Völker, Irene L. Andrulis, Håkan Olsson, Harry Campbell, Cari M. Kitahara, Annika Lindblom, Yvonne T. van der Schouw, Cinzia Sala, Debbie A Lawlor, Joe Dennis, Yongmei Liu, Yan Huang, Stephen Burgess, Brumat Marco, Veronique Vitart, Kari Stefansson, Susan E. Ozanne, Kamila Czene, Simin Liu, John L. Hopper, Joyce B. J. van Meurs, Satoshi H. Namekawa, Miya Kudo Høffding, Fergus J. Couch, Ajuna Azad, Eco J. C. de Geus, Liming Li, Grant W. Montgomery, Peter Kraft, André G. Uitterlinden, Arto Mannermaa, Heiko Becher, Allison W. Kurian, Vallari Shukla, Zhengming Chen, Per Hall, Jennifer A. Brody, Rossella Sorice, Wei Zhao, Andres Metspalu, Sarah E. Medland, Tricia Lindstrom, Clarice R. Weinberg, Bruce M. Psaty, Thérèse Truong, Anna Marie Mulligan, Deborah J. Thompson, Patrick Sulem, Internal Medicine, Epidemiology, Obstetrics & Gynecology, Hoffmann, Eva R [0000-0002-2588-0652], Murray, Anna [0000-0002-2351-2522], Roig, Ignasi [0000-0003-0313-3581], Perry, John RB [0000-0001-6483-3771], Apollo - University of Cambridge Repository, Life Course Epidemiology (LCE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), Biological Psychology, APH - Mental Health, APH - Methodology, APH - Personalized Medicine, and APH - Health Behaviors & Chronic Diseases
Subjects: Gerontology, Aging, Far East, Endocrinology, Diabetes and Metabolism, Menopause, Premature, Genome-wide association study, VARIANTS, Primary Ovarian Insufficiency, Inbred C57BL, Bioinformatics, DISEASE, Healthy Aging, genetics of ovarian aging, Fragile X Mental Retardation Protein, Mice, Endocrinology, Medicine, EARLY MENOPAUSE, media_common, RISK, Multidisciplinary, Asia, Eastern, Reproduction, Longevity, Middle Aged, Europe, MENDELIAN RANDOMIZATION, Medical genetics, Female, ICEP, Menopause, Adult, Alleles, Animals, Bone and Bones, Checkpoint Kinase 1, Checkpoint Kinase 2, Diabetes Mellitus, Type 2, Diet, Fertility, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Mice, Inbred C57BL, Ovary, Uterus, Type 2, medicine.medical_specialty, media_common.quotation_subject, MEDLINE, Biology, Premature ovarian insufficiency, Article, genome-wide meta-analysis, SDG 3 - Good Health and Well-being, GERMLINE, Diabetes Mellitus, Genetic predisposition, Ovarian reserve, Premature, business.industry, Human genetics, CHROMOSOME SYNAPSIS, DNA-DAMAGE, Ageing, EXPRESSION ANALYSIS, business, MEIOTIC CELL-CYCLE
Abstract: Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations3. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease. Hundreds of genetic loci associated with age at menopause, combined with experimental evidence in mice, highlight mechanisms of reproductive ageing across the lifespan.
Published: 2021
Full Text: View/download PDF

91. Cohabitation is associated with a greater resemblance in gut microbiota which can impact cardiometabolic and inflammatory risk

Author: Christel M. Davis, Erik A. Ehli, Dorret I. Boomsma, Gareth E. Davies, Casey T. Finnicum, Jeffrey J. Beck, Gonneke Willemsen, Conor V. Dolan, Eco J. C. de Geus, Biological Psychology, APH - Methodology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, and APH - Personalized Medicine
Subjects: Microbiology (medical), Adult, Male, Netherlands Twin Register (NTR), Intraclass correlation, lcsh:QR1-502, Cohabitation, Gut microbiota, Twin genetics, Biology, Gut flora, Microbiology, behavioral disciplines and activities, lcsh:Microbiology, Genetic profile, Correlation, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Humans, Spouses, Phylogeny, 030304 developmental biology, Aged, Netherlands, Genetics, Inflammation, 0303 health sciences, Bacteria, Significant difference, Sequence Analysis, DNA, Twins, Monozygotic, social sciences, Middle Aged, biology.organism_classification, Gastrointestinal Microbiome, Spouse, Cardiovascular Diseases, Female, 030217 neurology & neurosurgery, Biomarkers, Research Article
Abstract: Background The gut microbiota composition is known to be influenced by a myriad of factors including the host genetic profile and a number of environmental influences. Here, we focus on the environmental influence of cohabitation on the gut microbiota as well as whether these environmentally influenced microorganisms are associated with cardiometabolic and inflammatory burden. We perform this by investigating the gut microbiota composition of various groups of related individuals including cohabitating monozygotic (MZ) twin pairs, non-cohabitating MZ twin pairs and spouse pairs. Results A stronger correlation between alpha diversity was found in cohabitating MZ twins (45 pairs, r = 0.64, p = 2.21 × 10− 06) than in non-cohabitating MZ twin pairs (121 pairs, r = 0.42, p = 1.35 × 10− 06). Although the correlation of alpha diversity did not attain significance between spouse pairs (42 pairs, r = 0.23, p = 0.15), the correlation was still higher than those in the 209 unrelated pairs (r = − 0.015, p = 0.832). Bray-Curtis (BC) dissimilarity metrics showed cohabitating MZ twin pairs had the most similar gut microbiota communities which were more similar than the BC values of non-cohabitating MZ twins (empirical p-value = 0.0103), cohabitating spouses (empirical p-value = 0.0194), and pairs of unrelated non-cohabitating individuals (empirical p-valuep-value Conclusions Through the comparison of the microbiota contents of MZ twins with varying cohabitation status and spousal pairs, we showed evidence of environmentally influenced OTUs, one of which had a significant association with cardiometabolic and inflammatory burden scores.
Published: 2019
Full Text: View/download PDF

92. Phenome-wide investigation of health outcomes associated with genetic predisposition to loneliness

Author: Abraham A. Palmer, Dorret I. Boomsma, Sandra Sanchez-Roige, Jouke-Jan Hottenga, Alexander Neumann, Stephanie Cacioppo, Damiaan Denys, Gonneke Willemsen, Jorien L. Treur, Abdel Abdellaoui, Najaf Amin, Michel G. Nivard, Miriam A. Mosing, John T. Cacioppo, Julia Sealock, Bart M. L. Baselmans, Hill F. Ip, Karin J. H. Verweij, I. Szilagyi, Jessica Dennis, Sarah L. Elson, Henning Tiemeier, Matthijs D. van der Zee, Yi Lu, Cornelia M. van Duijn, Pierre Fontanillas, Lea K. Davis, Nancy L. Pedersen, Epidemiology, Psychiatry, Child and Adolescent Psychiatry / Psychology, Adult Psychiatry, ANS - Compulsivity, Impulsivity & Attention, APH - Mental Health, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Social Psychology, and APH - Methodology
Subjects: 0301 basic medicine, Netherlands Twin Register (NTR), Male, Multifactorial Inheritance, Genotype, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Mendelian randomization, Genetics, Genetic predisposition, medicine, Humans, Genetic Predisposition to Disease, Phenomics, Association Studies Article, Molecular Biology, Genetics (clinical), Loneliness, Mental Disorders, Mendelian Randomization Analysis, General Medicine, Mental health, Genetic architecture, 3. Good health, 030104 developmental biology, Mental Health, Phenotype, Health, Marital status, Female, medicine.symptom, 030217 neurology & neurosurgery, Clinical psychology, Genome-Wide Association Study
Abstract: Humans are social animals that experience intense suffering when they perceive a lack of social connection. Modern societies are experiencing an epidemic of loneliness. Although the experience of loneliness is universally human, some people report experiencing greater loneliness than others. Loneliness is more strongly associated with mortality than obesity, emphasizing the need to understand the nature of the relationship between loneliness and health. Although it is intuitive that circumstantial factors such as marital status and age influence loneliness, there is also compelling evidence of a genetic predisposition toward loneliness. To better understand the genetic architecture of loneliness and its relationship with associated outcomes, we extended the genome-wide association study meta-analysis of loneliness to 511 280 subjects, and detect 19 significant genetic variants from 16 loci, including four novel loci, as well as 58 significantly associated genes. We investigated the genetic overlap with a wide range of physical and mental health traits by computing genetic correlations and by building loneliness polygenic scores in an independent sample of 18 498 individuals with EHR data to conduct a PheWAS with. A genetic predisposition toward loneliness was associated with cardiovascular, psychiatric, and metabolic disorders and triglycerides and high-density lipoproteins. Mendelian randomization analyses showed evidence of a causal, increasing, the effect of both BMI and body fat on loneliness. Our results provide a framework for future studies of the genetic basis of loneliness and its relationship to mental and physical health.
Published: 2019
Full Text: View/download PDF

93. Neighbourhood characteristics and prevalence and severity of depression

Author: Petra J. M. Elders, Johannes H. Smit, Gonneke Willemsen, Ron de Graaf, Brenda W.J.H. Penninx, Eric Koomen, Mariska Stam, Erik J. Timmermans, Jeroen Lakerveld, Mirjam Oosterman, Karien Stronks, Sophia E. Kramer, Celina E Henke, Ellen Generaal, Marieke B. Snijder, Emiel O. Hoogendijk, Martijn Huisman, Dorret I. Boomsma, Femke Rutters, Margreet ten Have, APH - Methodology, APH - Health Behaviors & Chronic Diseases, Public and occupational health, APH - Aging & Later Life, ACS - Heart failure & arrhythmias, APH - Mental Health, LEARN! - Social cognition and learning, Clinical Child and Family Studies, The Social Context of Aging (SoCA), Sociology, Spatial Economics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Biological Psychology, Psychiatry, Epidemiology and Data Science, Otolaryngology / Head & Neck Surgery, Pediatric surgery, APH - Societal Participation & Health, General practice, VU University medical center, Amsterdam Reproduction & Development (AR&D), APH - Quality of Care, APH - Digital Health, and ACS - Diabetes & metabolism
Subjects: Adult, Male, Netherlands Twin Register (NTR), Adolescent, Poison control, Social Environment, Suicide prevention, Occupational safety and health, 03 medical and health sciences, Young Adult, 0302 clinical medicine, cohort studies, Residence Characteristics, Injury prevention, Prevalence, Medicine, Humans, 030212 general & internal medicine, Socioeconomic status, Neighbourhood (mathematics), Netherlands, geographic information systems, Depressive Disorder, business.industry, Depression, Odds ratio, Middle Aged, SDG 11 - Sustainable Cities and Communities, 030227 psychiatry, Psychiatry and Mental health, Cross-Sectional Studies, Socioeconomic Factors, Papers, Regression Analysis, Female, Mental health, business, environment, neighbourhood, Demography, Cohort study
Abstract: BackgroundStudies on neighbourhood characteristics and depression show equivocal results.AimsThis large-scale pooled analysis examines whether urbanisation, socioeconomic, physical and social neighbourhood characteristics are associated with the prevalence and severity of depression.MethodCross-sectional design including data are from eight Dutch cohort studies (n= 32 487). Prevalence of depression, either DSM-IV diagnosis of depressive disorder or scoring for moderately severe depression on symptom scales, and continuous depression severity scores were analysed. Neighbourhood characteristics were linked using postal codes and included (a) urbanisation grade, (b) socioeconomic characteristics: socioeconomic status, home value, social security beneficiaries and non-Dutch ancestry, (c) physical characteristics: air pollution, traffic noise and availability of green space and water, and (d) social characteristics: social cohesion and safety. Multilevel regression analyses were adjusted for the individual's age, gender, educational level and income. Cohort-specific estimates were pooled using random-effects analysis.ResultsThe pooled analysis showed that higher urbanisation grade (odds ratio (OR) = 1.05, 95% CI 1.01–1.10), lower socioeconomic status (OR = 0.90, 95% CI 0.87–0.95), higher number of social security beneficiaries (OR = 1.12, 95% CI 1.06–1.19), higher percentage of non-Dutch residents (OR = 1.08, 95% CI 1.02–1.14), higher levels of air pollution (OR = 1.07, 95% CI 1.01–1.12), less green space (OR = 0.94, 95% CI 0.88–0.99) and less social safety (OR = 0.92, 95% CI 0.88–0.97) were associated with higher prevalence of depression. All four socioeconomic neighbourhood characteristics and social safety were also consistently associated with continuous depression severity scores.ConclusionsThis large-scale pooled analysis across eight Dutch cohort studies shows that urbanisation and various socioeconomic, physical and social neighbourhood characteristics are associated with depression, indicating that a wide range of environmental aspects may relate to poor mental health.Declaration of interestNone.
Published: 2019
Full Text: View/download PDF

94. Associations between Loneliness and Personality are Mostly Driven by a Genetic Association with Neuroticism

Author: Gareth E. Davies, John T. Cacioppo, Eco J. C. de Geus, Gonneke Willemsen, Hsi-Yuan Chen, Erik A. Ehli, Michel G. Nivard, Abdel Abdellaoui, Karin J. H. Verweij, Dorret I. Boomsma, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Methodology, and Adult Psychiatry
Subjects: Adult, Male, 0301 basic medicine, Netherlands Twin Register (NTR), Adolescent, Social Psychology, media_common.quotation_subject, 050109 social psychology, Polymorphism, Single Nucleotide, Genetic correlation, Article, Young Adult, 03 medical and health sciences, medicine, Humans, Personality, 0501 psychology and cognitive sciences, Longitudinal Studies, Registries, Big Five personality traits, Aged, Netherlands, media_common, Aged, 80 and over, Neuroticism, Extraversion and introversion, Loneliness, 05 social sciences, Assortative mating, SDG 10 - Reduced Inequalities, Middle Aged, Twin study, Phenotype, 030104 developmental biology, Female, medicine.symptom, Psychology, Clinical psychology
Abstract: OBJECTIVE: Loneliness is an aversive response to a discrepancy between desired and actual social relationships and correlates with personality. We investigate the relationship of loneliness and personality in twin-family and molecular genetic data.METHOD: Phenotypic correlations between loneliness and the Big Five personality traits were estimated in 29,625 adults, and in a group with genome-wide genotype data (N=4,222), genetic correlations were obtained. We explored whether genetic correlations may reflect causal relationships by investigating within monozygotic twin-pair differences (Npairs =2,662), by longitudinal within-subject changes in personality and loneliness (N=4,260-9,238 longitudinal comparisons), and by longitudinal cross-lagged panel analyses (N=15,628). Finally, we tested whether genetic correlations were due to cross-trait assortative mating (Nspouse-pairs =4,436).RESULTS: The strongest correlations with loneliness were observed for neuroticism (r=.55) and extraversion (r=-.33). Only neuroticism showed a high correlation with loneliness independent of other personality traits (r=.50), so follow-up analyses focused on neuroticism. The genetic correlation between loneliness and neuroticism from genotyped variants was .71; a significant reciprocal causal relationship and non-significant cross-trait assortative mating imply that this is at least partly due to mediated pleiotropy.CONCLUSION: We show that the relationship between loneliness and personality is largely explained by its relationship with neuroticism, which is substantially genetic in nature. This article is protected by copyright. All rights reserved.
Published: 2019
Full Text: View/download PDF

95. Epigenome-wide association study of left-handedness for different tissues and ages

Author: Jouke-Jan Hottenga, Veronika V. Odintsova, Jenny van Dongen, Erik A. Ehli, Doretta Caramaschi, Fiona A. Hagenbeek, Jeffrey J. Beck, Gonneke Willemsen, René Pool, Dorret I. Boomsma, Catharina E. M. van Beijsterveldt, David M. Evans, Caroline L Relton, Eco J. C. de Geus, Gabriel Cuellar-Partida, Lannie Ligthart, Conor V. Dolan, Sarah E. Medland, and Matthew Sudermann
Subjects: Evolutionary biology, Epigenome, Biology, Association (psychology), Left handedness
Abstract: We report the first epigenome-wide association study of left-handedness, a trait with low heritability for which epigenetic mechanisms have been proposed as an underlying etiological mechanism. A region-based meta-analysis of whole blood genome-wide DNA methylation data from two cohorts (3,914 adults) identified differentially methylated regions annotated to BLCAP (20q11.23), a negative regulator of cell growth involved in apoptosis, NNAT (20q11.23), involved in brain development, and IAH1 (2p25.1), which encodes an acyl esterase. CpGs located in proximity to the SNPs from the largest GWAS of handedness were more strongly associated with left-handedness than other differentially methylated positions. In longitudinal whole blood samples, cord blood, and buccal cells from children (N = 1,967), the association with handedness displayed moderate stability across age, but little consistency across cell types. These findings suggest new candidate loci associated with handedness.
Published: 2021
Full Text: View/download PDF

96. The trans-ancestral genomic architecture of glycemic traits

Author: Albertine J. Oldehinkel, Wieland Kiess, Xueling Sim, Norihiro Kato, Philippe Froguel, Astrid van Hylckama Vlieg, Josée Dupuis, Nanette R. Lee, Symen Ligthart, Harry Campbell, Marta E. Alarcón-Riquelme, P. Eline Slagboom, Massimo Mangino, Tian Xie, Niek Verweij, James B. Meigs, Chaolong Wang, Michael Y. Tsai, Erik Ingelsson, Colin N. A. Palmer, Erik B. van den Akker, Fumihiko Matsuda, Rainer Rauramaa, Yi-Cheng Chang, Lars Lind, Stefan R. Bornstein, Mandy Vogel, Sven Bergmann, Ya X. Wang, Ching-Ti Liu, Annette Schürmann, Michael Boehnke, David J. Porteous, Kazuya Setoh, Qibin Qi, Ayse Demirkan, Francesco Cucca, Allan Linneberg, Claire J. Steves, Jun Liu, Leslie A. Lange, Noël P. Burtt, Diana Kuh, Cassandra N. Spracklen, Ken K. Ong, Charumathi Sabanayagam, Jost B. Jonas, Ele Ferrannini, Lawrence J. Beilin, Qing Duan, Blair H. Smith, Isobel D. Stewart, Alexander P. Reiner, Simon P. Mooijaart, Tim D. Spector, Paul W. Franks, E. Shyong Tai, Mark I. McCarthy, Anna L. Gloyn, D.I. Boomsma, Dennis Raven, Nicholas J. Timpson, Rona J. Strawbridge, George Dedoussis, Susan Redline, Jaeyoung Hong, Harald Grallert, Jagadish Vangipurapu, Rico Rueedi, Diane M. Becker, Marian Beekman, Claudia P. Cabrera, Johannes Waage, Jin Fang Chai, Yii-Der Ida Chen, Graciela E. Delgado, Thibaud S. Boutin, Yang Hai, Yoriko Heianza, Wei Zhao, Andres Metspalu, Tien Yin Wong, Mila Desi Anasanti, Inger Njølstad, Hans Bisgaard, Valeriya Lyssenko, Denis Rybin, Wanqing Wen, Torben Hansen, James F. Wilson, Sameline Grimsgaard, Annette Peters, Michele K. Evans, Damia Noce, Sarah C. Nelson, May E. Montasser, Nan Wang, Geltrude Mingrone, Gudny Eiriksdottir, Nicholas J. Wareham, Fouad Kandeel, Linda S. Adair, Kelvin Lam, Jaana Lindström, Eco J. C. de Geus, Debbie A Lawlor, Sara M. Willems, Xu Lin, Harold Snieder, Matt J. Neville, Naveed Sattar, Chelsea K. Raulerson, Paul M. Ridker, Jer-Yuarn Wu, Weihua Zhang, H. Janaka de Silva, Jana V. van Vliet-Ostaptchouk, Elena Tremoli, Toru Nabika, Jing Hua Zhao, Vilmundur Gudnason, Tao Huang, Robert C. Kaplan, Sohee Han, Mohammad Hadi Zafarmand, Aaron Leong, Yen-Feng Chiu, Kumaraswamy Naidu Chitrala, Ivana Kolcic, Franco Giulianini, Tao Wang, Lu Qi, Stephan J. L. Bakker, Laura J Corbin, Zoltán Kutalik, Bruna Gigante, Willa A. Hsueh, Peter J. van der Most, Tin Louie, Yujie Wang, Stella Trompet, Fernando Rivideneira, Yasumasa Ohyagi, Lynne E. Wagenknecht, Jerry L. Nadler, Michael Stumvoll, Mark O. Goodarzi, Sahoko Ichihara, Jeffrey R. O'Connell, Tomohiro Katsuya, Giorgio Pistis, Alice Stanton, Sirkka Keinänen-Kiukaanniemi, Momoko Horikoshi, Honglan Li, Tanja G. M. Vrijkotte, Caroline Hayward, Karen L. Mohlke, Carola Marzi, Girish N. Nadkarni, Laura J. Rasmussen-Torvik, Alain G. Bertoni, Andrew R. Wood, Annique Claringbould, Mi Yeong Hwang, Hugh Watkins, Heikki A. Koistinen, Mattias Frånberg, Jani Heikkinen, Elizabeth Selvin, Donald W. Bowden, Abbas Dehghan, Christian Fuchsberger, Audrey Y. Chu, Kent D. Taylor, Katherine A. Kentistou, Johanna Kuusisto, Jingyi Tan, Huaixing Li, Eric Boerwinkle, Catharina A. Hartman, Archie Campbell, Kari E. North, Oluf Pedersen, Sölve Elmståhl, Emil V. R. Appel, Chang-Hsun Hsieh, Dennis O. Mook-Kanamori, Rob M. van Dam, Pontiano Kaleebu, Corri Black, Jennifer A. Brody, Bengt Sennblad, Shaofeng Huo, M. Larissa Avilés-Santa, Ruth J. F. Loos, Patricia B. Munroe, Chien-Hsiun Chen, Liang Sun, Zorayr Arzumanyan, Rebecca Rohde, Yasuharu Tabara, Albert V. Smith, Betina H. Thuesen, Niels Grarup, Jorgen Engmann, Tatijana Zemunik, M. Arfan Ikram, Marit E. Jørgensen, Christian Herder, Ching-Yu Cheng, Serena Sanna, Damiano Baldassarre, Tarunveer S. Ahluwalia, Mark J. Caulfield, Anne Ndungu, Carl D. Langefeld, Lisa R. Yanek, Luigi Ferrucci, Ananda R. Wickremasinghe, Raymond Noordam, Trevor A. Mori, Tom Wilsgaard, Mika Kivimäki, Rita R. Kalyani, Alan B. Zonderman, Veronique Vitart, Patricia A. Peyser, Shuiqing Lai, Richa Saxena, Li-Ching Chang, Karin Leander, Wei Huang, Peter Vollenweider, Tanya M. Teslovich, Ying Wu, Shufa Du, Brian E. Cade, Patrik K. E. Magnusson, John C. Chambers, Stephen C. J. Parker, Tamar Sofer, Winfried März, Sharon L.R. Kardia, Peter K. Joshi, Neil R. Robertson, Anny H. Xiang, Fumihiko Takeuchi, N. Amin, Jouke-Jan Hottenga, Carol A. Wang, Stefan Gustafsson, Jung Ho Gong, Penny Gordon-Larsen, Yu-Tang Gao, Abhishek Nag, Gonneke Willemsen, Michael A. Province, Aliki-Eleni Farmaki, Segun Fatumo, Antje Körner, Pim van der Harst, Marie Loh, Kei Hang Katie Chan, Gonçalo R. Abecasis, Nicholette D. Palmer, Simin Liu, Ishminder K. Kooner, Javier Gayán, Arne Astrup, Laura J. Scott, Erwin P. Bottinger, Andrew Wong, Inga Prokopenko, Ping An, Markku Laakso, Matthias Blüher, Susan R. Heckbert, Thomas A. Buchanan, Tatsuaki Matsubara, Andrew P. Morris, Brian H. Chen, Kristi Läll, Teresa Tusie, Timo A. Lakka, Jie Yao, Michael Preuss, Teemu Kuulasmaa, Carlos Lorenzo, Stephen S. Rich, Marie Lauzon, Laura M. Raffield, Pankow S. James, Takahisa Kawaguchi, Kathleen A. Ryan, Wei Zheng, Igor Rudan, Thomas Sparsø, Hugoline G. de Haan, Sandosh Padmanabhan, Richard M. Watanabe, Alicia Huerta-Chagoya, Anette P. Gjesing, Andrew A. Hicks, Richard N. Bergman, Mitsuhiro Yokota, Heather M. Stringham, Bruce M. Psaty, Jian'an Luan, Anuj Goel, Eleanor Wheeler, Masahiro Nakatochi, Young-Jin Kim, Xiao-Ou Shu, Mickaël Canouil, Robert A. Scott, Marika Kaakinen, Mari Nelis, Adolfo Correa, Jaspal S. Kooner, Michiya Igase, Anubha Mahajan, Peter E. H. Schwarz, Craig E. Pennell, Claudia Schurmann, Xiaoran Chai, Ji Chen, Lori L. Bonnycastle, Peter S. Sever, Thorkild I. A. Sørensen, André G. Uitterlinden, Ilja M. Nolte, Gaëlle Marenne, Timothy M. Frayling, Bong-Jo Kim, Kerrin S. Small, Cecilia M. Lindgren, Bernhard O. Böhm, Shih-Yi Lin, Katharina E. Schraut, Cornelia M. van Duijn, Sanghoon Moon, Mark Walker, Chiea Chuen Khor, Ruifang Li-Gao, Qiuyin Cai, Neil Schneiderman, Ko Willems van Dijk, Ozren Polasek, W. Craig Johnson, Dermot F. Reilly, Inês Barroso, Anke Tönjes, Manjinder S. Sandhu, Wen B. Wei, Jose C. Florez, Lorraine Southam, Leif Groop, Lawrence F. Bielak, Peter Kovacs, Jianjun Liu, Jouko Saramies, Helen R. Warren, Man Li, Daniel I. Chasman, Eleftheria Zeggini, Xiaoshuai Zhang, Loic Yengo, Shi Jinxiu, Jirong Long, Xiuqing Guo, Meena Kumari, Leslie J. Raffel, Jill M. Norris, Henrik Vestergaard, Jing He, Peter P. Pramstaller, Diana van Heemst, Kevin Sandow, Marjo-Ritta Jarvelin, Carlos A. Aguilar-Salinas, Peitao Wu, Hortensia Moreno-Macías, Jerome I. Rotter, Kathryn Roll, Frits R. Rosendaal, Bernardo L. Horta, Heming Wang, Fernando Pires Hartwig, Richard A. Jensen, Matti Uusitupa, Rozenn N. Lemaitre, Paul R. H. J. Timmers, Timo Saaristo, Jaakko Tuomilehto, Reedik Mägi, Debashree Ray, J. Wouter Jukema, Claudia Langenberg, Marcus E. Kleber, Francis S. Collins, Klaus Bønnelykke, Lenore J. Launer, Arushi Varshney, Anders Hamsten, European Commission, Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Sanger Institute, Wellcome Trust, Marenne, Gaëlle [0000-0002-4363-7170], Varshney, Arushi [0000-0001-9177-9707], Corbin, Laura J [0000-0002-4032-9500], Parker, Stephen CJ [0000-0001-8122-0117], Langenberg, Claudia [0000-0002-5017-7344], Wheeler, Eleanor [0000-0002-8616-6444], Morris, Andrew P [0000-0002-6805-6014], Barroso, Inês [0000-0001-5800-4520], Apollo - University of Cambridge Repository, Lifelines Cohort Study, Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC), de Haan, H.G., van den Akker, E., van der Most, P.J., de Geus, EJC, van Dam, R.M., van Heemst, D., van Hylckama Vlieg, A., van Willems van Dijk, K., de Silva, H.J., van der Harst, P., van Duijn, C., Centre of Excellence in Complex Disease Genetics, HUS Abdominal Center, Institute for Molecular Medicine Finland, Leif Groop Research Group, HUS Internal Medicine and Rehabilitation, Department of Medicine, Department of Biochemistry and Developmental Biology, Helsinki University Hospital Area, University of Helsinki, Clinicum, Department of Public Health, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Physiology, AMS - Musculoskeletal Health, AMS - Tissue Function & Regeneration, APH - Mental Health, Nutrition and Health, APH - Methodology, Epidemiology and Data Science, ACS - Atherosclerosis & ischemic syndromes, APH - Aging & Later Life, ARD - Amsterdam Reproduction and Development, Public and occupational health, Epidemiology, Internal Medicine, Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Institute for Organ Transplantation (GIOT), Groningen Kidney Center (GKC), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Center for Liver, Digestive and Metabolic Diseases (CLDM), and Cardiovascular Centre (CVC)
Subjects: Blood Glucose, Disease risk, Multifactorial Inheritance, Glycated Hemoglobin A, [SDV]Life Sciences [q-bio], Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC), LOCI, Genome-wide association study, Type 2 diabetes, VARIANTS, GLUCOSE, Epigenesis, Genetic, chemistry.chemical_compound, 0302 clinical medicine, Mechanisms, WIDE ASSOCIATION, genetics, Gene-expression, HEMOGLOBIN, ComputingMilieux_MISCELLANEOUS, 11 Medical and Health Sciences, GENE-EXPRESSION, Genetics, Genetics & Heredity, 0303 health sciences, INSULIN-RESISTANCE, Genome, Loci, 1184 Genetics, developmental biology, physiology, Variants, ALSPAC, Physical Chromosome Mapping, Life Sciences & Biomedicine, Human, Quantitative Trait Loci, Wide association study, Biology, Quantitative trait locus, Article, White People, diseases, MECHANISMS, Quantitative Trait, 03 medical and health sciences, Insulin resistance, Quantitative Trait, Heritable, SDG 3 - Good Health and Well-being, Genetic, Lifelines Cohort Study, Diabetes mellitus, medicine, Humans, Hemoglobin, Heritable, METAANALYSIS, Alleles, 030304 developmental biology, Genetic association, Glycemic, Glycated Hemoglobin, Science & Technology, Genome, Human, Whites, Gene Expression Profiling, DISEASE RISK, Settore MED/13 - ENDOCRINOLOGIA, Insulin-resistance, 06 Biological Sciences, medicine.disease, Glucose, chemistry, Blood Glucose/genetics, European Continental Ancestry Group/genetics, Genome-Wide Association Study, Glycated Hemoglobin A/metabolism, Multifactorial Inheritance/genetics, Quantitative Trait Loci/genetics, Glycated hemoglobin, 030217 neurology & neurosurgery, Meta analysis, Epigenesis, Developmental Biology
Abstract: Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.
Published: 2021
Full Text: View/download PDF

97. Individual differences in the effect of the COVID-19 pandemic on optimism and meaning in life

Author: de Vries L, de Geus E, Gonneke Willemsen, Lannie Ligthart, Van de Weijer M, Meike Bartels, Dorret I. Boomsma, and Dirk H. M. Pelt
Subjects: Optimism, Coronavirus disease 2019 (COVID-19), media_common.quotation_subject, Pandemic, Meaning (existential), Psychology, media_common, Epistemology
Abstract: We investigated the effect of the COVID-19 pandemic and lockdown on optimism and meaning in life in a sample of the Netherlands Twin Register. Participants completed questions before (N=9964) and during the pandemic (N= 17464). A subsample completed both (N=6461). We applied twin models to investigate changes in the genetic architecture due to the pandemic.Around 15-20% of the sample was negatively affected by the pandemic, but the majority was stable (64-68%) or increased (15%) in optimism and meaning in life. Especially women, higher educated people, and people with poorer health experienced negative effects. Twin modelling indicated stable genetic variance and increasing person-specific environmental variance. The lower than unity genetic correlations across time (.75 and .63) suggest gene-environment interactions.Some people decrease in well-being, while others get more optimistic and consider their lives as more meaningful during the pandemic. These differences are partly explained by individual differences in genetic sensitivity.
Published: 2021
Full Text: View/download PDF

98. Genetic insights into the biological mechanisms governing human ovarian ageing

Author: Unnur Styrkarsdottir, Daniel I. Chasman, Rehannah Borup, Anne B. Newman, Kristina W. Olsen, Lude Franke, Stefania Bandinelli, Nora Franceschini, Celine M. Vachon, Nicholas J. Timpson, James F. Wilson, Micaella Joaquim, Christa Meisinger, Felix R. Day, Charles Kooperberg, Qin Wang, Pascal Timshel, Dennis O. Mook-Kanamori, Luigi Ferrucci, Jennifer A. Smith, Miriam Dwek, Pascal Guénel, Claus Yding Andersen, Peter A. Fasching, Sven Bergmann, Thomas Meitinger, Nicholas Bowker, Jane L. Tarry-Adkins, Jeremy A. Daniel, Katharina E. Schraut, Mikael Eriksson, Amruta Shrikhande, Jacques E. Rossouw, Amber N. Wilcox, Simon S. Cross, Stasa Stankovic, Montserrat Garcia-Closas, Mohammad Arfan Ikram, Annette Peters, David Schlessinger, Sheila Ulivi, Mònica Ferrer-Roda, Immaculata De Vivo, Michela Traglia, Jessica Tyrrell, Paul R. H. J. Timmers, Rico Rueedi, Ko Willems van Dijk, N. Charlotte Onland-Moret, Doris Stöckl, Anthony J. Swerdlow, Paul M. Ridker, Zoltán Kutalik, Patrick Deelen, Gerardo Heiss, Marie Louise Grøndahl, Alison M. Dunning, Dale R. Nyholt, Nicholas J. Wareham, Reedik Mägi, Stephen J. Chanock, Martina La Bianca, Ozren Polasek, Daniel F. Gudbjartsson, Rebecca D. Jackson, Alison D. Murray, Lynda M. Rose, Hironori Abe, Joanne M. Murabito, Henry Völzke, Daniela Ruggiero, Dorret I. Boomsma, Harald Grallert, Stefania Benonisdottir, Javier Martin Gonzalez, Esther M. John, Natalia Perjakova, Georgia Chenevix-Trench, John R. B. Perry, Jenny Chang-Claude, Archie Campbell, Teresa Nutile, Ellen W. Demerath, Robin N Beaumont, Jouke J. Hottenga, Albert V. Smith, David Karasik, Linda Broer, Raymond Noordam, Wei He, Niclas Håkansson, Catherine E. Aiken, Robert Karlsson, Christopher A. Haiman, Massimo Mangino, Melissa C. Southey, Sharon L.R. Kardia, Nicholas G. Martin, Jodie N. Painter, Peter K. Joshi, Gonneke Willemsen, Lenore J. Launer, Alicja Wolk, Konstantin Strauch, Stig E. Bojesen, Manjeet K. Bolla, Allison W. Kurian, Renée de Mutsert, Joop S.E. Laven, Antonella Mulas, Igor Rudan, Vallari Shukla, Kathyrn L Lunetta, Susan E. Ozanne, Loic Le Marchand, Jenny A. Visser, Gad Rennert, Jennifer A. Brody, Paul D.P. Pharoah, Tune H. Pers, Sara Lindström, Ignasi Roig, Angela Cox, Unnur Þorsteinsdottir, Graham G. Giles, Toshiko Tanaka, Eva Hoffmann, Melissa A. Troester, Claudia Langenberg, Serena Sanna, Julie E. Buring, Anna Pujol, Mike A. Nalls, Kamila Czene, Tõnu Esko, Jian'an Luan, Lili Milani, Iffat Rahman, Sarah E. Medland, Caterina Barbieri, Emil Peter Trane Hertz, Behrooz Z. Alizadeh, David G. Hunter, Sandra Turon, Antonietta Robino, Marina Ciullo, Barbara McKnight, Chunyan He, Bruce H. R. Wolffenbuttel, David R. Weir, Daniela Toniolo, Ulrike Peters, George Davey-Smith, Saleh Shekari, Caroline Hayward, Elinor J. Sawyer, Patrick Sulem, Simin Liu, Tanguy Corre, Susan M. Ring, Peter Kraft, Alexander Teumer, Marjanka K. Schmidt, André G. Uitterlinden, Arto Mannermaa, Kristan J. Aronson, Heiko Becher, John L. Hopper, Alpa V. Patel, Joyce B. J. van Meurs, kConFab Investigators, Hamdi Mbarek, Frits R. Rosendaal, Minouk J. Schoemaker, Satoshi H. Namekawa, Miya Kudo Høffding, Fergus J. Couch, Nancy L. Pedersen, Jessica D. Faul, Patrik K. E. Magnusson, Jingmei Li, Christopher G. Scott, Joe Dennis, Genevieve Lachance, Ajuna Azad, Yongmei Liu, Elnaz Naderi, Andrew R. Wood, Yan Huang, Anna Murray, Annique Claringbould, Stephen Burgess, Jose E. Castelao, Brumat Marco, Eco J. C. de Geus, Veronique Vitart, Ken K. Ong, Kari Stefansson, Blair H. Smith, Francesco Cucca, Grant W. Montgomery, Emmanouil Saloustros, Andrés J. López-Contreras, Jonathan Marten, Håkan Olsson, Dale P. Sandler, Alice M. Arnold, Ana Martínez-Marchal, Tim D. Spector, Chloé Sarnowski, John J. Spinelli, Vilmundur Gudnason, Frank B. Hu, Thomas U. Ahearn, Hedy S. Rennert, Olivier B. Bakker, Eric Boerwinkle, Matthias W. Beckmann, Jazib Hussain, Uwe Völker, Peter Vollenweider, Douglas F. Easton, Irene L. Andrulis, Harry Campbell, Manuela Gago-Dominguez, Cari M. Kitahara, Yvonne T. van der Schouw, Eleonora Porcu, Annika Lindblom, Martha S. Linet, Meir J. Stampfer, Eulalia Catamo, Roger L. Milne, Ivana Kolcic, Annelie Augustinsson, Cinzia Sala, Debbie A Lawlor, Cristina Menni, Timothy M. Frayling, Lauren R. Teras, Marek Zygmunt, Tricia Lindstrom, Clarice R. Weinberg, Bruce M. Psaty, Thérèse Truong, Anna Marie Mulligan, Deborah J. Thompson, Per Hall, Rossella Sorice, Wei Zhao, Andres Metspalu, Katherine S. Ruth, Andrew F. Olshan, Massimo Mezzavilla, Murielle Bochud, and Christian Gieger
Subjects: media_common.quotation_subject, Genetic predisposition, Longevity, Fertility, Disease, Biology, Premature ovarian insufficiency, Bioinformatics, Ovarian reserve, FMR1, Human genetics, media_common
Abstract: Reproductive longevity is critical for fertility and impacts healthy ageing in women, yet insights into the underlying biological mechanisms and treatments to preserve it are limited. Here, we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in ∼200,000 women of European ancestry. These common alleles influence clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenicFMR1premutations. Identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increase fertility and extend reproductive life in mice. Causal inference analyses using the identified genetic variants indicates that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases risks of hormone-sensitive cancers. These findings provide insight into the mechanisms governing ovarian ageing, when they act across the life-course, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.
Published: 2021
Full Text: View/download PDF

99. A Comparison of Ten Polygenic Score Methods for Psychiatric Disorders Applied Across Multiple Cohorts

Author: Guiyan Ni, Jian Zeng, Joana A. Revez, Ying Wang, Zhili Zheng, Tian Ge, Restuadi Restuadi, Jacqueline Kiewa, Dale R. Nyholt, Jonathan R.I. Coleman, Jordan W. Smoller, Jian Yang, Peter M. Visscher, Naomi R. Wray, Stephan Ripke, Benjamin M. Neale, Aiden Corvin, James T.R. Walters, Kai-How Farh, Peter A. Holmans, Phil Lee, Brendan Bulik-Sullivan, David A. Collier, Hailiang Huang, Tune H. Pers, Ingrid Agartz, Esben Agerbo, Margot Albus, Madeline Alexander, Farooq Amin, Silviu A. Bacanu, Martin Begemann, Richard A. Belliveau, Judit Bene, Sarah E. Bergen, Elizabeth Bevilacqua, Tim B. Bigdeli, Donald W. Black, Richard Bruggeman, Nancy G. Buccola, Randy L. Buckner, William Byerley, Wiepke Cahn, Guiqing Cai, Dominique Campion, Rita M. Cantor, Vaughan J. Carr, Noa Carrera, Stanley V. Catts, Kimberley D. Chambert, Raymond C.K. Chan, Ronald Y.L. Chen, Eric Y.H. Chen, Wei Cheng, Eric F.C. Cheung, Siow Ann Chong, C. Robert Cloninger, David Cohen, Nadine Cohen, Paul Cormican, Nick Craddock, James J. Crowley, Michael Davidson, Kenneth L. Davis, Franziska Degenhardt, Jurgen Del Favero, Ditte Demontis, Dimitris Dikeos, Timothy Dinan, Srdjan Djurovic, Gary Donohoe, Elodie Drapeau, Jubao Duan, Frank Dudbridge, Naser Durmishi, Peter Eichhammer, Johan Eriksson, Valentina Escott-Price, Laurent Essioux, Ayman H. Fanous, Martilias S. Farrell, Josef Frank, Lude Franke, Robert Freedman, Nelson B. Freimer, Marion Friedl, Joseph I. Friedman, Menachem Fromer, Giulio Genovese, Lyudmila Georgieva, Ina Giegling, Paola Giusti-Rodríguez, Stephanie Godard, Jacqueline I. Goldstein, Vera Golimbet, Srihari Gopal, Jacob Gratten, Lieuwe de Haan, Christian Hammer, Marian L. Hamshere, Mark Hansen, Thomas Hansen, Vahram Haroutunian, Annette M. Hartmann, Frans A. Henskens, Stefan Herms, Joel N. Hirschhorn, Per Hoffmann, Andrea Hofman, Mads V. Hollegaard, David M. Hougaard, Masashi Ikeda, Inge Joa, Antonio Julià, René S. Kahn, Luba Kalaydjieva, Sena Karachanak-Yankova, Juha Karjalainen, David Kavanagh, Matthew C. Keller, James L. Kennedy, Andrey Khrunin, Yunjung Kim, Janis Klovins, James A. Knowles, Bettina Konte, Vaidutis Kucinskas, Zita Ausrele Kucinskiene, Hana Kuzelova-Ptackova, Anna K. Kähler, Claudine Laurent, Jimmy Lee, S. Hong Lee, Sophie E. Legge, Bernard Lerer, Miaoxin Li, Tao Li, Kung-Yee Liang, Jeffrey Lieberman, Svetlana Limborska, Carmel M. Loughland, Jan Lubinski, Jouko Lönnqvist, Milan Macek, Patrik K.E. Magnusson, Brion S. Maher, Wolfgang Maier, Jacques Mallet, Sara Marsal, Manuel Mattheisen, Morten Mattingsdal, Robert W. McCarley, Colm McDonald, Andrew M. McIntosh, Sandra Meier, Carin J. Meijer, Bela Melegh, Ingrid Melle, Raquelle I. Mesholam-Gately, Andres Metspalu, Patricia T. Michie, Lili Milani, Vihra Milanova, Younes Mokrab, Derek W. Morris, Ole Mors, Kieran C. Murphy, Robin M. Murray, Inez Myin-Germeys, Bertram Müller-Myhsok, Mari Nelis, Igor Nenadic, Deborah A. Nertney, Gerald Nestadt, Kristin K. Nicodemus, Liene Nikitina-Zake, Laura Nisenbaum, Annelie Nordin, Eadbhard O’Callaghan, Colm O’Dushlaine, F. Anthony O’Neill, Sang-Yun Oh, Ann Olincy, Line Olsen, Jim Van Os, Psychosis Endophenotypes International Consortium, Christos Pantelis, George N. Papadimitriou, Sergi Papiol, Elena Parkhomenko, Michele T. Pato, Tiina Paunio, Milica Pejovic-Milovancevic, Diana O. Perkins, Olli Pietiläinen, Jonathan Pimm, Andrew J. Pocklington, John Powell, Alkes Price, Ann E. Pulver, Shaun M. Purcell, Digby Quested, Henrik B. Rasmussen, Abraham Reichenberg, Mark A. Reimers, Alexander L. Richards, Joshua L. Roffman, Panos Roussos, Douglas M. Ruderfer, Veikko Salomaa, Alan R. Sanders, Ulrich Schall, Christian R. Schubert, Thomas G. Schulze, Sibylle G. Schwab, Edward M. Scolnick, Rodney J. Scott, Larry J. Seidman, Jianxin Shi, Engilbert Sigurdsson, Teimuraz Silagadze, Jeremy M. Silverman, Kang Sim, Petr Slominsky, Hon-Cheong So, Chris C.A. Spencer, Eli A. Stahl, Hreinn Stefansson, Stacy Steinberg, Elisabeth Stogmann, Richard E. Straub, Eric Strengman, Jana Strohmaier, T. Scott Stroup, Mythily Subramaniam, Jaana Suvisaari, Dragan M. Svrakic, Jin P. Szatkiewicz, Erik Söderman, Srinivas Thirumalai, Draga Toncheva, Sarah Tosato, Juha Veijola, John Waddington, Dermot Walsh, Dai Wang, Qiang Wang, Bradley T. Webb, Mark Weiser, Dieter B. Wildenauer, Nigel M. Williams, Stephanie Williams, Stephanie H. Witt, Aaron R. Wolen, Emily H.M. Wong, Brandon K. Wormley, Hualin Simon Xi, Clement C. Zai, Xuebin Zheng, Fritz Zimprich, Kari Stefansson, Wellcome Trust Case-Control Consortium, Rolf Adolfsson, Ole A. Andreassen, Douglas H.R. Blackwood, Elvira Bramon, Joseph D. Buxbaum, Anders D. Børglum, Sven Cichon, Ariel Darvasi, Enrico Domenici, Hannelore Ehrenreich, Tõnu Esko, Pablo V. Gejman, Michael Gill, Hugh Gurling, Christina M. Hultman, Nakao Iwata, Assen V. Jablensky, Erik G. Jönsson, Kenneth S. Kendler, George Kirov, Jo Knight, Todd Lencz, Douglas F. Levinson, Qingqin S. Li, Jianjun Liu, Anil K. Malhotra, Steven A. McCarroll, Andrew McQuillin, Jennifer L. Moran, Preben B. Mortensen, Bryan J. Mowry, Markus M. Nöthen, Roel A. Ophoff, Michael J. Owen, Aarno Palotie, Carlos N. Pato, Tracey L. Petryshen, Danielle Posthuma, Marcella Rietschel, Brien P. Riley, Dan Rujescu, Pak C. Sham, Pamela Sklar, David St Clair, Daniel R. Weinberger, Jens R. Wendland, Thomas Werge, Mark J. Daly, Patrick F. Sullivan, Michael C. O’Donovan, Maciej Trzaskowski, Enda M. Byrne, Abdel Abdellaoui, Mark J. Adams, Tracy M. Air, Till F.M. Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T.F. Beekman, Elisabeth B. Binder, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Enrique Castelao, Jane Hvarregaard Christensen, Toni-Kim Clarke, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Gregory E. Crawford, Gail Davies, Ian J. Deary, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Jerome C. Foo, Andreas J. Forstner, Héléna A. Gaspar, Fernando S. Goes, Scott D. Gordon, Jakob Grove, Lynsey S. Hall, Christine Søholm Hansen, Thomas F. Hansen, Ian B. Hickie, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Howard, Marcus Ising, Rick Jansen, Ian Jones, Lisa A. Jones, Eric Jorgenson, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Donald J. MacIntyre, Dean F. MacKinnon, Robert M. Maier, Jonathan Marchini, Hamdi Mbarek, Patrick McGrath, Peter McGuffin, Sarah E. Medland, Divya Mehta, Christel M. Middeldorp, Evelin Mihailov, Yuri Milaneschi, Francis M. Mondimore, Grant W. Montgomery, Sara Mostafavi, Niamh Mullins, Matthias Nauck, Bernard Ng, Michel G. Nivard, Paul F. O’Reilly, Hogni Oskarsson, Jodie N. Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E. Peterson, Wouter J. Peyrot, Giorgio Pistis, Jorge A. Quiroz, Per Qvist, John P. Rice, Margarita Rivera, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Stanley I. Shyn, Grant C.B. Sinnamon, Johannes H. Smit, Daniel J. Smith, Fabian Streit, Katherine E. Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A. Thomson, Thorgeir E. Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G. Uitterlinden, Daniel Umbricht, Sandra Van der Auwera, Albert M. van Hemert, Alexander Viktorin, Yunpeng Wang, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Yang Wu, Hualin S. Xi, Futao Zhang, Volker Arolt, Bernhard T. Baune, Klaus Berger, Dorret I. Boomsma, Udo Dannlowski, E.J.C. de Geus, J. Raymond DePaulo, Katharina Domschke, Hans J. Grabe, Steven P. Hamilton, Caroline Hayward, Andrew C. Heath, Stefan Kloiber, Glyn Lewis, Susanne Lucae, Pamela A.F. Madden, Patrik K. Magnusson, Nicholas G. Martin, Preben Bo Mortensen, Merete Nordentoft, Sara A. Paciga, Nancy L. Pedersen, Adult Psychiatry, APH - Mental Health, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Ni, Guiyan, Zeng, Jian, Revez, Joana A., Wang, Ying, Zhili, Zheng, Ge, Tian, Restuadi, Restuadi, Kiewa, Jacqueline, Nyholt, Dale R, Coleman, Jonathan RI, Smoller, Jordan W, Lee, S Hong, APH - Methodology, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Econometrics, Psychiatry, Department of Technology and Operations Management, Child and Adolescent Psychiatry / Psychology, Epidemiology, Erasmus MC other, Urology, Internal Medicine, Medical Informatics, Immunology, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Reproduction & Development (AR&D), and Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep
Subjects: 0301 basic medicine, Multifactorial Inheritance, medicine.medical_specialty, LDpred2, BF, Genomics, Disease, Major depressive disorder, risk prediction, 03 medical and health sciences, 0302 clinical medicine, MegaPRS, SDG 3 - Good Health and Well-being, medicine, Humans, Genetic Predisposition to Disease, ddc:610, Genetic risk, Psychiatry, Biological Psychiatry, Genetic association, Depressive Disorder, Major, business.industry, Mental Disorders, medicine.disease, Genetic architecture, Polygenic scores, Risk prediction, polygenic scores, PRS-CS, psychiatric disorders, 030104 developmental biology, SBayesR, Schizophrenia, Cohort, Lassosum, RC0321, business, Psychiatric disorders, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: BACKGROUND: Polygenic scores (PGSs), which assess the genetic risk of individuals for a disease, are calculated as a weighted count of risk alleles identified in genome-wide association studies. PGS methods differ in which DNA variants are included and the weights assigned to them; some require an independent tuning sample to help inform these choices. PGSs are evaluated in independent target cohorts with known disease status. Variability between target cohorts is observed in applications to real data sets, which could reflect a number of factors, e.g., phenotype definition or technical factors.METHODS: The Psychiatric Genomics Consortium Working Groups for schizophrenia and major depressive disorder bring together many independently collected case-control cohorts. We used these resources (31,328 schizophrenia cases, 41,191 controls; 248,750 major depressive disorder cases, 563,184 controls) in repeated application of leave-one-cohort-out meta-analyses, each used to calculate and evaluate PGS in the left-out (target) cohort. Ten PGS methods (the baseline PC+T method and 9 methods that model genetic architecture more formally: SBLUP, LDpred2-Inf, LDpred-funct, LDpred2, Lassosum, PRS-CS, PRS-CS-auto, SBayesR, MegaPRS) were compared.RESULTS: Compared with PC+T, the other 9 methods gave higher prediction statistics, MegaPRS, LDPred2, and SBayesR significantly so, explaining up to 9.2% variance in liability for schizophrenia across 30 target cohorts, an increase of 44%. For major depressive disorder across 26 target cohorts, these statistics were 3.5% and 59%, respectively.CONCLUSIONS: Although the methods that more formally model genetic architecture have similar performance, MegaPRS, LDpred2, and SBayesR rank highest in most comparisons and are recommended in applications to psychiatric disorders.
Published: 2021
Full Text: View/download PDF

100. Large-scale association analyses identify host factors influencing human gut microbiome composition

Author: Jordana T. Bell, Sara Vieira-Silva, Torben Hansen, Andrew D. Paterson, Nicholas J. Timpson, Robert C. Kaplan, Vincent W. V. Jaddoe, Fabian Frost, Gwen Falony, Zachary D. Wallen, Mauro D'Amato, David A. Hughes, Jakob Stokholm, Lude Franke, Matthew A. Jackson, Marc Jan Bonder, Gonneke Willemsen, Dmitrii Borisevich, Hocheol Shin, Kyoko Watanabe, Annique Claringbould, Joanna Szopinska-Tokov, Markus M. Lerch, Caroline I. Le Roy, Markku Laakso, Eran Segal, Daisy Jonkers, Jee-Young Moon, Williams Turpin, Susanna Walter, Xingrong Liu, Lars Agréus, Tim D. Spector, Malte C. Rühlemann, Raul Y. Tito, Daniel Keszthelyi, Gareth E. Davies, Shiraz A. Shah, Ad A.M. Masclee, Carolina Medina-Gomez, Kreete Lüll, Robert D. Burk, Elin Org, Matthias Laudes, Cornelia M. van Duijn, Myriam Fornage, Urmo Võsa, Oluf Pedersen, Lenore J. Launer, Kaitlin H Wade, Juan Antonio Raygoza Garay, Rob Knight, Elad Barkan, Daria V. Zhernakova, Michael Boehnke, Frank Ulrich Weiss, Andre Franke, Jonathan Thorsen, Henry Völzke, Jingyuan Fu, Fernando Rivadeneira, Daphna Rothschild, Robert Kraaij, Katie A. Meyer, Ayse Demirkan, Claire J. Steves, Stefan Weiss, Cisca Wijmenga, Hans Bisgaard, Qi Qibin, Corinna Bang, Rodrigo Bacigalupe, Haydeh Payami, Han-Na Kim, Liesbeth Duijts, Alexander Kurilshikov, Serena Sanna, Kenneth Croitoru, Jeroen Raes, Djawad Radjabzadeh, Eco J. C. de Geus, Jun Wang, Richard G. IJzerman, Harm-Jan Westra, Uwe Völker, Torben Jørgensen, Dorret I. Boomsma, Omer Weissbrod, Alexandra Zhernakova, Alejandro Arias Vasquez, Casey T. Finnicum, Hyung Lae Kim, Marie Joossens, Tue H. Hansen, Henriette A. Moll, Anna Andreasson, Larbi Bedrani, Zlatan Mujagic, Adriaan van der Graaf, Søren J. Sørensen, Aldons J. Lusis, Wolfgang Lieb, Georg Homuth, André G. Uitterlinden, Biological Psychology, APH - Mental Health, APH - Methodology, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, APH - Health Behaviors & Chronic Diseases, Interne Geneeskunde, RS: NUTRIM - R2 - Liver and digestive health, MUMC+: MA Maag Darm Lever (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Internal Medicine, Epidemiology, Pediatrics, Erasmus MC other, Center for Liver, Digestive and Metabolic Diseases (CLDM), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), Translational Immunology Groningen (TRIGR), Internal medicine, ACS - Diabetes & metabolism, and Amsterdam Gastroenterology Endocrinology Metabolism
Subjects: Male, Linkage disequilibrium, Genome-wide association study, Genome-wide association studies, Medical and Health Sciences, Oral and gastrointestinal, Linkage Disequilibrium, Cohort Studies, 0302 clinical medicine, RNA, Ribosomal, 16S, 2.1 Biological and endogenous factors, Aetiology, Child, Lactase, Genetics & Heredity, 2. Zero hunger, Genetics, 0303 health sciences, Biological Sciences, Child, Preschool, MENDELIAN RANDOMIZATION, Female, Life Sciences & Biomedicine, Biotechnology, Adult, 16S, Adolescent, Quantitative Trait Loci, Locus (genetics), Biology, Quantitative trait locus, GENOTYPE IMPUTATION, Microbiology, metagenome, Article, diseases, 03 medical and health sciences, Clinical Research, Genetic variation, Mendelian randomization, Humans, Microbiome, Preschool, Nutrition, 030304 developmental biology, Ribosomal, ecosystem, ENVIRONMENT, Science & Technology, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], IDENTIFICATION, Human Genome, Genetic Variation, Mendelian Randomization Analysis, FRAMEWORK, Gastrointestinal Microbiome, Metabolism, Metagenomics, genome-wide association, RNA, Bifidobacterium, Digestive Diseases, 030217 neurology & neurosurgery, Developmental Biology, Genome-Wide Association Study
Abstract: Contains fulltext : 231681.pdf (Publisher’s version ) (Closed access) To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P
Published: 2021
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

538 results on '"Gonneke Willemsen"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources