Author: "Gonneke Willemsen" / Publisher: public library of science (plos) - Searchworks@Jio Institute Digital Library Search Results

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34 results on '"Gonneke Willemsen"'

1. Integrative network analysis highlights biological processes underlying GLP-1 stimulated insulin secretion: A DIRECT study.

Author: Valborg Gudmundsdottir, Helle Krogh Pedersen, Karla Viviani Allebrandt, Caroline Brorsson, Nienke van Leeuwen, Karina Banasik, Anubha Mahajan, Christopher J Groves, Martijn van de Bunt, Adem Y Dawed, Andreas Fritsche, Harald Staiger, Annemarie M C Simonis-Bik, Joris Deelen, Mark H H Kramer, Axel Dietrich, Thomas Hübschle, Gonneke Willemsen, Hans-Ulrich Häring, Eco J C de Geus, Dorret I Boomsma, Elisabeth M W Eekhoff, Jorge Ferrer, Mark I McCarthy, Ewan R Pearson, Ramneek Gupta, Søren Brunak, and Leen M 't Hart
Subjects: Medicine, Science
Abstract: Glucagon-like peptide 1 (GLP-1) stimulated insulin secretion has a considerable heritable component as estimated from twin studies, yet few genetic variants influencing this phenotype have been identified. We performed the first genome-wide association study (GWAS) of GLP-1 stimulated insulin secretion in non-diabetic individuals from the Netherlands Twin register (n = 126). This GWAS was enhanced using a tissue-specific protein-protein interaction network approach. We identified a beta-cell protein-protein interaction module that was significantly enriched for low gene scores based on the GWAS P-values and found support at the network level in an independent cohort from Tübingen, Germany (n = 100). Additionally, a polygenic risk score based on SNPs prioritized from the network was associated (P < 0.05) with glucose-stimulated insulin secretion phenotypes in up to 5,318 individuals in MAGIC cohorts. The network contains both known and novel genes in the context of insulin secretion and is enriched for members of the focal adhesion, extracellular-matrix receptor interaction, actin cytoskeleton regulation, Rap1 and PI3K-Akt signaling pathways. Adipose tissue is, like the beta-cell, one of the target tissues of GLP-1 and we thus hypothesized that similar networks might be functional in both tissues. In order to verify peripheral effects of GLP-1 stimulation, we compared the transcriptome profiling of ob/ob mice treated with liraglutide, a clinically used GLP-1 receptor agonist, versus baseline controls. Some of the upstream regulators of differentially expressed genes in the white adipose tissue of ob/ob mice were also detected in the human beta-cell network of genes associated with GLP-1 stimulated insulin secretion. The findings provide biological insight into the mechanisms through which the effects of GLP-1 may be modulated and highlight a potential role of the beta-cell expressed genes RYR2, GDI2, KIAA0232, COL4A1 and COL4A2 in GLP-1 stimulated insulin secretion.
Published: 2018
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2. Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis.

Author: Eleanor Wheeler, Aaron Leong, Ching-Ti Liu, Marie-France Hivert, Rona J Strawbridge, Clara Podmore, Man Li, Jie Yao, Xueling Sim, Jaeyoung Hong, Audrey Y Chu, Weihua Zhang, Xu Wang, Peng Chen, Nisa M Maruthur, Bianca C Porneala, Stephen J Sharp, Yucheng Jia, Edmond K Kabagambe, Li-Ching Chang, Wei-Min Chen, Cathy E Elks, Daniel S Evans, Qiao Fan, Franco Giulianini, Min Jin Go, Jouke-Jan Hottenga, Yao Hu, Anne U Jackson, Stavroula Kanoni, Young Jin Kim, Marcus E Kleber, Claes Ladenvall, Cecile Lecoeur, Sing-Hui Lim, Yingchang Lu, Anubha Mahajan, Carola Marzi, Mike A Nalls, Pau Navarro, Ilja M Nolte, Lynda M Rose, Denis V Rybin, Serena Sanna, Yuan Shi, Daniel O Stram, Fumihiko Takeuchi, Shu Pei Tan, Peter J van der Most, Jana V Van Vliet-Ostaptchouk, Andrew Wong, Loic Yengo, Wanting Zhao, Anuj Goel, Maria Teresa Martinez Larrad, Dörte Radke, Perttu Salo, Toshiko Tanaka, Erik P A van Iperen, Goncalo Abecasis, Saima Afaq, Behrooz Z Alizadeh, Alain G Bertoni, Amelie Bonnefond, Yvonne Böttcher, Erwin P Bottinger, Harry Campbell, Olga D Carlson, Chien-Hsiun Chen, Yoon Shin Cho, W Timothy Garvey, Christian Gieger, Mark O Goodarzi, Harald Grallert, Anders Hamsten, Catharina A Hartman, Christian Herder, Chao Agnes Hsiung, Jie Huang, Michiya Igase, Masato Isono, Tomohiro Katsuya, Chiea-Chuen Khor, Wieland Kiess, Katsuhiko Kohara, Peter Kovacs, Juyoung Lee, Wen-Jane Lee, Benjamin Lehne, Huaixing Li, Jianjun Liu, Stephane Lobbens, Jian'an Luan, Valeriya Lyssenko, Thomas Meitinger, Tetsuro Miki, Iva Miljkovic, Sanghoon Moon, Antonella Mulas, Gabriele Müller, Martina Müller-Nurasyid, Ramaiah Nagaraja, Matthias Nauck, James S Pankow, Ozren Polasek, Inga Prokopenko, Paula S Ramos, Laura Rasmussen-Torvik, Wolfgang Rathmann, Stephen S Rich, Neil R Robertson, Michael Roden, Ronan Roussel, Igor Rudan, Robert A Scott, William R Scott, Bengt Sennblad, David S Siscovick, Konstantin Strauch, Liang Sun, Morris Swertz, Salman M Tajuddin, Kent D Taylor, Yik-Ying Teo, Yih Chung Tham, Anke Tönjes, Nicholas J Wareham, Gonneke Willemsen, Tom Wilsgaard, Aroon D Hingorani, EPIC-CVD Consortium, EPIC-InterAct Consortium, Lifelines Cohort Study, Josephine Egan, Luigi Ferrucci, G Kees Hovingh, Antti Jula, Mika Kivimaki, Meena Kumari, Inger Njølstad, Colin N A Palmer, Manuel Serrano Ríos, Michael Stumvoll, Hugh Watkins, Tin Aung, Matthias Blüher, Michael Boehnke, Dorret I Boomsma, Stefan R Bornstein, John C Chambers, Daniel I Chasman, Yii-Der Ida Chen, Yduan-Tsong Chen, Ching-Yu Cheng, Francesco Cucca, Eco J C de Geus, Panos Deloukas, Michele K Evans, Myriam Fornage, Yechiel Friedlander, Philippe Froguel, Leif Groop, Myron D Gross, Tamara B Harris, Caroline Hayward, Chew-Kiat Heng, Erik Ingelsson, Norihiro Kato, Bong-Jo Kim, Woon-Puay Koh, Jaspal S Kooner, Antje Körner, Diana Kuh, Johanna Kuusisto, Markku Laakso, Xu Lin, Yongmei Liu, Ruth J F Loos, Patrik K E Magnusson, Winfried März, Mark I McCarthy, Albertine J Oldehinkel, Ken K Ong, Nancy L Pedersen, Mark A Pereira, Annette Peters, Paul M Ridker, Charumathi Sabanayagam, Michele Sale, Danish Saleheen, Juha Saltevo, Peter Eh Schwarz, Wayne H H Sheu, Harold Snieder, Timothy D Spector, Yasuharu Tabara, Jaakko Tuomilehto, Rob M van Dam, James G Wilson, James F Wilson, Bruce H R Wolffenbuttel, Tien Yin Wong, Jer-Yuarn Wu, Jian-Min Yuan, Alan B Zonderman, Nicole Soranzo, Xiuqing Guo, David J Roberts, Jose C Florez, Robert Sladek, Josée Dupuis, Andrew P Morris, E-Shyong Tai, Elizabeth Selvin, Jerome I Rotter, Claudia Langenberg, Inês Barroso, and James B Meigs
Subjects: Medicine
Abstract: BackgroundGlycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes.Methods & findingsUsing genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 × 10-29); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI 0.55-0.74) of African American adults with T2D to remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants.ConclusionsAs G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.
Published: 2017
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3. Correction: Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults.

Author: Mariaelisa Graff, Robert A Scott, Anne E Justice, Kristin L Young, Mary F Feitosa, Llilda Barata, Thomas W Winkler, Audrey Y Chu, Anubha Mahajan, David Hadley, Luting Xue, Tsegaselassie Workalemahu, Nancy L Heard-Costa, Marcel den Hoed, Tarunveer S Ahluwalia, Qibin Qi, Julius S Ngwa, Frida Renström, Lydia Quaye, John D Eicher, James E Hayes, Marilyn Cornelis, Zoltan Kutalik, Elise Lim, Jian'an Luan, Jennifer E Huffman, Weihua Zhang, Wei Zhao, Paula J Griffin, Toomas Haller, Shafqat Ahmad, Pedro M Marques-Vidal, Stephanie Bien, Loic Yengo, Alexander Teumer, Albert Vernon Smith, Meena Kumari, Marie Neergaard Harder, Johanne Marie Justesen, Marcus E Kleber, Mette Hollensted, Kurt Lohman, Natalia V Rivera, John B Whitfield, Jing Hua Zhao, Heather M Stringham, Leo-Pekka Lyytikäinen, Charlotte Huppertz, Gonneke Willemsen, Wouter J Peyrot, Ying Wu, Kati Kristiansson, Ayse Demirkan, Myriam Fornage, Maija Hassinen, Lawrence F Bielak, Gemma Cadby, Toshiko Tanaka, Reedik Mägi, Peter J van der Most, Anne U Jackson, Jennifer L Bragg-Gresham, Veronique Vitart, Jonathan Marten, Pau Navarro, Claire Bellis, Dorota Pasko, Åsa Johansson, Søren Snitker, Yu-Ching Cheng, Joel Eriksson, Unhee Lim, Mette Aadahl, Linda S Adair, Najaf Amin, Beverley Balkau, Juha Auvinen, John Beilby, Richard N Bergman, Sven Bergmann, Alain G Bertoni, John Blangero, Amélie Bonnefond, Lori L Bonnycastle, Judith B Borja, Søren Brage, Fabio Busonero, Steve Buyske, Harry Campbell, Peter S Chines, Francis S Collins, Tanguy Corre, George Davey Smith, Graciela E Delgado, Nicole Dueker, Marcus Dörr, Tapani Ebeling, Gudny Eiriksdottir, Tõnu Esko, Jessica D Faul, Mao Fu, Kristine Færch, Christian Gieger, Sven Gläser, Jian Gong, Penny Gordon-Larsen, Harald Grallert, Tanja B Grammer, Niels Grarup, Gerard van Grootheest, Kennet Harald, Nicholas D Hastie, Aki S Havulinna, Dena Hernandez, Lucia Hindorff, Lynne J Hocking, Oddgeir L Holmens, Christina Holzapfel, Jouke Jan Hottenga, Jie Huang, Tao Huang, Jennie Hui, Cornelia Huth, Nina Hutri-Kähönen, Alan L James, John-Olov Jansson, Min A Jhun, Markus Juonala, Leena Kinnunen, Heikki A Koistinen, Ivana Kolcic, Pirjo Komulainen, Johanna Kuusisto, Kirsti Kvaløy, Mika Kähönen, Timo A Lakka, Lenore J Launer, Benjamin Lehne, Cecilia M Lindgren, Mattias Lorentzon, Robert Luben, Michel Marre, Yuri Milaneschi, Keri L Monda, Grant W Montgomery, Marleen H M De Moor, Antonella Mulas, Martina Müller-Nurasyid, A W Musk, Reija Männikkö, Satu Männistö, Narisu Narisu, Matthias Nauck, Jennifer A Nettleton, Ilja M Nolte, Albertine J Oldehinkel, Matthias Olden, Ken K Ong, Sandosh Padmanabhan, Lavinia Paternoster, Jeremiah Perez, Markus Perola, Annette Peters, Ulrike Peters, Patricia A Peyser, Inga Prokopenko, Hannu Puolijoki, Olli T Raitakari, Tuomo Rankinen, Laura J Rasmussen-Torvik, Rajesh Rawal, Paul M Ridker, Lynda M Rose, Igor Rudan, Cinzia Sarti, Mark A Sarzynski, Kai Savonen, William R Scott, Serena Sanna, Alan R Shuldiner, Steve Sidney, Günther Silbernagel, Blair H Smith, Jennifer A Smith, Harold Snieder, Alena Stančáková, Barbara Sternfeld, Amy J Swift, Tuija Tammelin, Sian-Tsung Tan, Barbara Thorand, Dorothée Thuillier, Liesbeth Vandenput, Henrik Vestergaard, Jana V van Vliet-Ostaptchouk, Marie-Claude Vohl, Uwe Völker, Gérard Waeber, Mark Walker, Sarah Wild, Andrew Wong, Alan F Wright, M Carola Zillikens, Niha Zubair, Christopher A Haiman, Loic Lemarchand, Ulf Gyllensten, Claes Ohlsson, Albert Hofman, Fernando Rivadeneira, André G Uitterlinden, Louis Pérusse, James F Wilson, Caroline Hayward, Ozren Polasek, Francesco Cucca, Kristian Hveem, Catharina A Hartman, Anke Tönjes, Stefania Bandinelli, Lyle J Palmer, Sharon L R Kardia, Rainer Rauramaa, Thorkild I A Sørensen, Jaakko Tuomilehto, Veikko Salomaa, Brenda W J H Penninx, Eco J C de Geus, Dorret I Boomsma, Terho Lehtimäki, Massimo Mangino, Markku Laakso, Claude Bouchard, Nicholas G Martin, Diana Kuh, Yongmei Liu, Allan Linneberg, Winfried März, Konstantin Strauch, Mika Kivimäki, Tamara B Harris, Vilmundur Gudnason, Henry Völzke, Lu Qi, Marjo-Riitta Järvelin, John C Chambers, Jaspal S Kooner, Philippe Froguel, Charles Kooperberg, Peter Vollenweider, Göran Hallmans, Torben Hansen, Oluf Pedersen, Andres Metspalu, Nicholas J Wareham, Claudia Langenberg, David R Weir, David J Porteous, Eric Boerwinkle, Daniel I Chasman, CHARGE Consortium, EPIC-InterAct Consortium, PAGE Consortium, Gonçalo R Abecasis, Inês Barroso, Mark I McCarthy, Timothy M Frayling, Jeffrey R O'Connell, Cornelia M van Duijn, Michael Boehnke, Iris M Heid, Karen L Mohlke, David P Strachan, Caroline S Fox, Ching-Ti Liu, Joel N Hirschhorn, Robert J Klein, Andrew D Johnson, Ingrid B Borecki, Paul W Franks, Kari E North, L Adrienne Cupples, Ruth J F Loos, and Tuomas O Kilpeläinen
Subjects: Genetics, QH426-470
Abstract: [This corrects the article DOI: 10.1371/journal.pgen.1006528.].
Published: 2017
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4. Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults.

Author: Mariaelisa Graff, Robert A Scott, Anne E Justice, Kristin L Young, Mary F Feitosa, Llilda Barata, Thomas W Winkler, Audrey Y Chu, Anubha Mahajan, David Hadley, Luting Xue, Tsegaselassie Workalemahu, Nancy L Heard-Costa, Marcel den Hoed, Tarunveer S Ahluwalia, Qibin Qi, Julius S Ngwa, Frida Renström, Lydia Quaye, John D Eicher, James E Hayes, Marilyn Cornelis, Zoltan Kutalik, Elise Lim, Jian'an Luan, Jennifer E Huffman, Weihua Zhang, Wei Zhao, Paula J Griffin, Toomas Haller, Shafqat Ahmad, Pedro M Marques-Vidal, Stephanie Bien, Loic Yengo, Alexander Teumer, Albert Vernon Smith, Meena Kumari, Marie Neergaard Harder, Johanne Marie Justesen, Marcus E Kleber, Mette Hollensted, Kurt Lohman, Natalia V Rivera, John B Whitfield, Jing Hua Zhao, Heather M Stringham, Leo-Pekka Lyytikäinen, Charlotte Huppertz, Gonneke Willemsen, Wouter J Peyrot, Ying Wu, Kati Kristiansson, Ayse Demirkan, Myriam Fornage, Maija Hassinen, Lawrence F Bielak, Gemma Cadby, Toshiko Tanaka, Reedik Mägi, Peter J van der Most, Anne U Jackson, Jennifer L Bragg-Gresham, Veronique Vitart, Jonathan Marten, Pau Navarro, Claire Bellis, Dorota Pasko, Åsa Johansson, Søren Snitker, Yu-Ching Cheng, Joel Eriksson, Unhee Lim, Mette Aadahl, Linda S Adair, Najaf Amin, Beverley Balkau, Juha Auvinen, John Beilby, Richard N Bergman, Sven Bergmann, Alain G Bertoni, John Blangero, Amélie Bonnefond, Lori L Bonnycastle, Judith B Borja, Søren Brage, Fabio Busonero, Steve Buyske, Harry Campbell, Peter S Chines, Francis S Collins, Tanguy Corre, George Davey Smith, Graciela E Delgado, Nicole Dueker, Marcus Dörr, Tapani Ebeling, Gudny Eiriksdottir, Tõnu Esko, Jessica D Faul, Mao Fu, Kristine Færch, Christian Gieger, Sven Gläser, Jian Gong, Penny Gordon-Larsen, Harald Grallert, Tanja B Grammer, Niels Grarup, Gerard van Grootheest, Kennet Harald, Nicholas D Hastie, Aki S Havulinna, Dena Hernandez, Lucia Hindorff, Lynne J Hocking, Oddgeir L Holmens, Christina Holzapfel, Jouke Jan Hottenga, Jie Huang, Tao Huang, Jennie Hui, Cornelia Huth, Nina Hutri-Kähönen, Alan L James, John-Olov Jansson, Min A Jhun, Markus Juonala, Leena Kinnunen, Heikki A Koistinen, Ivana Kolcic, Pirjo Komulainen, Johanna Kuusisto, Kirsti Kvaløy, Mika Kähönen, Timo A Lakka, Lenore J Launer, Benjamin Lehne, Cecilia M Lindgren, Mattias Lorentzon, Robert Luben, Michel Marre, Yuri Milaneschi, Keri L Monda, Grant W Montgomery, Marleen H M De Moor, Antonella Mulas, Martina Müller-Nurasyid, A W Musk, Reija Männikkö, Satu Männistö, Narisu Narisu, Matthias Nauck, Jennifer A Nettleton, Ilja M Nolte, Albertine J Oldehinkel, Matthias Olden, Ken K Ong, Sandosh Padmanabhan, Lavinia Paternoster, Jeremiah Perez, Markus Perola, Annette Peters, Ulrike Peters, Patricia A Peyser, Inga Prokopenko, Hannu Puolijoki, Olli T Raitakari, Tuomo Rankinen, Laura J Rasmussen-Torvik, Rajesh Rawal, Paul M Ridker, Lynda M Rose, Igor Rudan, Cinzia Sarti, Mark A Sarzynski, Kai Savonen, William R Scott, Serena Sanna, Alan R Shuldiner, Steve Sidney, Günther Silbernagel, Blair H Smith, Jennifer A Smith, Harold Snieder, Alena Stančáková, Barbara Sternfeld, Amy J Swift, Tuija Tammelin, Sian-Tsung Tan, Barbara Thorand, Dorothée Thuillier, Liesbeth Vandenput, Henrik Vestergaard, Jana V van Vliet-Ostaptchouk, Marie-Claude Vohl, Uwe Völker, Gérard Waeber, Mark Walker, Sarah Wild, Andrew Wong, Alan F Wright, M Carola Zillikens, Niha Zubair, Christopher A Haiman, Loic Lemarchand, Ulf Gyllensten, Claes Ohlsson, Albert Hofman, Fernando Rivadeneira, André G Uitterlinden, Louis Pérusse, James F Wilson, Caroline Hayward, Ozren Polasek, Francesco Cucca, Kristian Hveem, Catharina A Hartman, Anke Tönjes, Stefania Bandinelli, Lyle J Palmer, Sharon L R Kardia, Rainer Rauramaa, Thorkild I A Sørensen, Jaakko Tuomilehto, Veikko Salomaa, Brenda W J H Penninx, Eco J C de Geus, Dorret I Boomsma, Terho Lehtimäki, Massimo Mangino, Markku Laakso, Claude Bouchard, Nicholas G Martin, Diana Kuh, Yongmei Liu, Allan Linneberg, Winfried März, Konstantin Strauch, Mika Kivimäki, Tamara B Harris, Vilmundur Gudnason, Henry Völzke, Lu Qi, Marjo-Riitta Järvelin, John C Chambers, Jaspal S Kooner, Philippe Froguel, Charles Kooperberg, Peter Vollenweider, Göran Hallmans, Torben Hansen, Oluf Pedersen, Andres Metspalu, Nicholas J Wareham, Claudia Langenberg, David R Weir, David J Porteous, Eric Boerwinkle, Daniel I Chasman, CHARGE Consortium, EPIC-InterAct Consortium, PAGE Consortium, Gonçalo R Abecasis, Inês Barroso, Mark I McCarthy, Timothy M Frayling, Jeffrey R O'Connell, Cornelia M van Duijn, Michael Boehnke, Iris M Heid, Karen L Mohlke, David P Strachan, Caroline S Fox, Ching-Ti Liu, Joel N Hirschhorn, Robert J Klein, Andrew D Johnson, Ingrid B Borecki, Paul W Franks, Kari E North, L Adrienne Cupples, Ruth J F Loos, and Tuomas O Kilpeläinen
Subjects: Genetics, QH426-470
Abstract: Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
Published: 2017
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5. Relative Telomere Repeat Mass in Buccal and Leukocyte-Derived DNA.

Author: Casey T Finnicum, Conor V Dolan, Gonneke Willemsen, Zachary M Weber, Jason L Petersen, Jeffrey J Beck, Veryan Codd, Dorret I Boomsma, Gareth E Davies, and Erik A Ehli
Subjects: Medicine, Science
Abstract: Telomere length has garnered interest due to the potential role it may play as a biomarker for the cellular aging process. Telomere measurements obtained from blood-derived DNA are often used in epidemiological studies. However, the invasive nature of blood draws severely limits sample collection, particularly with children. Buccal cells are commonly sampled for DNA isolation and thus may present a non-invasive alternative for telomere measurement. Buccal and leukocyte derived DNA obtained from samples collected at the same time period were analyzed for telomere repeat mass (TRM). TRM was measured in buccal-derived DNA samples from individuals for whom previous TRM data from blood samples existed. TRM measurement was performed by qPCR and was normalized to the single copy 36B4 gene relative to a reference DNA sample (K562). Correlations between TRM from blood and buccal DNA were obtained and also between the same blood DNA samples measured in separate laboratories. Using the classical twin design, TRM heritability was estimated (N = 1892, MZ = 1044, DZ = 775). Buccal samples measured for TRM showed a significant correlation with the blood-1 (R = 0.39, p < 0.01) and blood-2 (R = 0.36, p < 0.01) samples. Sex and age effects were observed within the buccal samples as is the norm within blood-derived DNA. The buccal, blood-1, and blood-2 measurements generated heritability estimates of 23.3%, 47.6% and 22.2%, respectively. Buccal derived DNA provides a valid source for the determination of TRM, paving the way for non-invasive projects, such as longitudinal studies in children.
Published: 2017
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6. Correction: The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.

Author: Thomas W Winkler, Anne E Justice, Mariaelisa Graff, Llilda Barata, Mary F Feitosa, Su Chu, Jacek Czajkowski, Tõnu Esko, Tove Fall, Tuomas O Kilpeläinen, Yingchang Lu, Reedik Mägi, Evelin Mihailov, Tune H Pers, Sina Rüeger, Alexander Teumer, Georg B Ehret, Teresa Ferreira, Nancy L Heard-Costa, Juha Karjalainen, Vasiliki Lagou, Anubha Mahajan, Michael D Neinast, Inga Prokopenko, Jeannette Simino, Tanya M Teslovich, Rick Jansen, Harm-Jan Westra, Charles C White, Devin Absher, Tarunveer S Ahluwalia, Shafqat Ahmad, Eva Albrecht, Alexessander Couto Alves, Jennifer L Bragg-Gresham, Anton J M de Craen, Joshua C Bis, Amélie Bonnefond, Gabrielle Boucher, Gemma Cadby, Yu-Ching Cheng, Charleston W K Chiang, Graciela Delgado, Ayse Demirkan, Nicole Dueker, Niina Eklund, Gudny Eiriksdottir, Joel Eriksson, Bjarke Feenstra, Krista Fischer, Francesca Frau, Tessel E Galesloot, Frank Geller, Anuj Goel, Mathias Gorski, Tanja B Grammer, Stefan Gustafsson, Saskia Haitjema, Jouke-Jan Hottenga, Jennifer E Huffman, Anne U Jackson, Kevin B Jacobs, Åsa Johansson, Marika Kaakinen, Marcus E Kleber, Jari Lahti, Irene Mateo Leach, Benjamin Lehne, Youfang Liu, Ken Sin Lo, Mattias Lorentzon, Jian'an Luan, Pamela A F Madden, Massimo Mangino, Barbara McKnight, Carolina Medina-Gomez, Keri L Monda, May E Montasser, Gabriele Müller, Martina Müller-Nurasyid, Ilja M Nolte, Kalliope Panoutsopoulou, Laura Pascoe, Lavinia Paternoster, Nigel W Rayner, Frida Renström, Federica Rizzi, Lynda M Rose, Kathy A Ryan, Perttu Salo, Serena Sanna, Hubert Scharnagl, Jianxin Shi, Albert Vernon Smith, Lorraine Southam, Alena Stančáková, Valgerdur Steinthorsdottir, Rona J Strawbridge, Yun Ju Sung, Ioanna Tachmazidou, Toshiko Tanaka, Gudmar Thorleifsson, Stella Trompet, Natalia Pervjakova, Jonathan P Tyrer, Liesbeth Vandenput, Sander W van der Laan, Nathalie van der Velde, Jessica van Setten, Jana V van Vliet-Ostaptchouk, Niek Verweij, Efthymia Vlachopoulou, Lindsay L Waite, Sophie R Wang, Zhaoming Wang, Sarah H Wild, Christina Willenborg, James F Wilson, Andrew Wong, Jian Yang, Loïc Yengo, Laura M Yerges-Armstrong, Lei Yu, Weihua Zhang, Jing Hua Zhao, Ehm A Andersson, Stephan J L Bakker, Damiano Baldassarre, Karina Banasik, Matteo Barcella, Cristina Barlassina, Claire Bellis, Paola Benaglio, John Blangero, Matthias Blüher, Fabrice Bonnet, Lori L Bonnycastle, Heather A Boyd, Marcel Bruinenberg, Aron S Buchman, Harry Campbell, Yii-Der Ida Chen, Peter S Chines, Simone Claudi-Boehm, John Cole, Francis S Collins, Eco J C de Geus, Lisette C P G M de Groot, Maria Dimitriou, Jubao Duan, Stefan Enroth, Elodie Eury, Aliki-Eleni Farmaki, Nita G Forouhi, Nele Friedrich, Pablo V Gejman, Bruna Gigante, Nicola Glorioso, Alan S Go, Omri Gottesman, Jürgen Gräßler, Harald Grallert, Niels Grarup, Yu-Mei Gu, Linda Broer, Annelies C Ham, Torben Hansen, Tamara B Harris, Catharina A Hartman, Maija Hassinen, Nicholas Hastie, Andrew T Hattersley, Andrew C Heath, Anjali K Henders, Dena Hernandez, Hans Hillege, Oddgeir Holmen, Kees G Hovingh, Jennie Hui, Lise L Husemoen, Nina Hutri-Kähönen, Pirro G Hysi, Thomas Illig, Philip L De Jager, Shapour Jalilzadeh, Torben Jørgensen, J Wouter Jukema, Markus Juonala, Stavroula Kanoni, Maria Karaleftheri, Kay Tee Khaw, Leena Kinnunen, Steven J Kittner, Wolfgang Koenig, Ivana Kolcic, Peter Kovacs, Nikolaj T Krarup, Wolfgang Kratzer, Janine Krüger, Diana Kuh, Meena Kumari, Theodosios Kyriakou, Claudia Langenberg, Lars Lannfelt, Chiara Lanzani, Vaneet Lotay, Lenore J Launer, Karin Leander, Jaana Lindström, Allan Linneberg, Yan-Ping Liu, Stéphane Lobbens, Robert Luben, Valeriya Lyssenko, Satu Männistö, Patrik K Magnusson, Wendy L McArdle, Cristina Menni, Sigrun Merger, Lili Milani, Grant W Montgomery, Andrew P Morris, Narisu Narisu, Mari Nelis, Ken K Ong, Aarno Palotie, Louis Pérusse, Irene Pichler, Maria G Pilia, Anneli Pouta, Myriam Rheinberger, Rasmus Ribel-Madsen, Marcus Richards, Kenneth M Rice, Treva K Rice, Carlo Rivolta, Veikko Salomaa, Alan R Sanders, Mark A Sarzynski, Salome Scholtens, Robert A Scott, William R Scott, Sylvain Sebert, Sebanti Sengupta, Bengt Sennblad, Thomas Seufferlein, Angela Silveira, P Eline Slagboom, Jan H Smit, Thomas H Sparsø, Kathleen Stirrups, Ronald P Stolk, Heather M Stringham, Morris A Swertz, Amy J Swift, Ann-Christine Syvänen, Sian-Tsung Tan, Barbara Thorand, Anke Tönjes, Angelo Tremblay, Emmanouil Tsafantakis, Peter J van der Most, Uwe Völker, Marie-Claude Vohl, Judith M Vonk, Melanie Waldenberger, Ryan W Walker, Roman Wennauer, Elisabeth Widén, Gonneke Willemsen, Tom Wilsgaard, Alan F Wright, M Carola Zillikens, Suzanne C van Dijk, Natasja M van Schoor, Folkert W Asselbergs, Paul I W de Bakker, Jacques S Beckmann, John Beilby, David A Bennett, Richard N Bergman, Sven Bergmann, Carsten A Böger, Bernhard O Boehm, Eric Boerwinkle, Dorret I Boomsma, Stefan R Bornstein, Erwin P Bottinger, Claude Bouchard, John C Chambers, Stephen J Chanock, Daniel I Chasman, Francesco Cucca, Daniele Cusi, George Dedoussis, Jeanette Erdmann, Johan G Eriksson, Denis A Evans, Ulf de Faire, Martin Farrall, Luigi Ferrucci, Ian Ford, Lude Franke, Paul W Franks, Philippe Froguel, Ron T Gansevoort, Christian Gieger, Henrik Grönberg, Vilmundur Gudnason, Ulf Gyllensten, Per Hall, Anders Hamsten, Pim van der Harst, Caroline Hayward, Markku Heliövaara, Christian Hengstenberg, Andrew A Hicks, Aroon Hingorani, Albert Hofman, Frank Hu, Heikki V Huikuri, Kristian Hveem, Alan L James, Joanne M Jordan, Antti Jula, Mika Kähönen, Eero Kajantie, Sekar Kathiresan, Lambertus A L M Kiemeney, Mika Kivimaki, Paul B Knekt, Heikki A Koistinen, Jaspal S Kooner, Seppo Koskinen, Johanna Kuusisto, Winfried Maerz, Nicholas G Martin, Markku Laakso, Timo A Lakka, Terho Lehtimäki, Guillaume Lettre, Douglas F Levinson, Lars Lind, Marja-Liisa Lokki, Pekka Mäntyselkä, Mads Melbye, Andres Metspalu, Braxton D Mitchell, Frans L Moll, Jeffrey C Murray, Arthur W Musk, Markku S Nieminen, Inger Njølstad, Claes Ohlsson, Albertine J Oldehinkel, Ben A Oostra, Lyle J Palmer, James S Pankow, Gerard Pasterkamp, Nancy L Pedersen, Oluf Pedersen, Brenda W Penninx, Markus Perola, Annette Peters, Ozren Polašek, Peter P Pramstaller, Bruce M Psaty, Lu Qi, Thomas Quertermous, Olli T Raitakari, Tuomo Rankinen, Rainer Rauramaa, Paul M Ridker, John D Rioux, Fernando Rivadeneira, Jerome I Rotter, Igor Rudan, Hester M den Ruijter, Juha Saltevo, Naveed Sattar, Heribert Schunkert, Peter E H Schwarz, Alan R Shuldiner, Juha Sinisalo, Harold Snieder, Thorkild I A Sørensen, Tim D Spector, Jan A Staessen, Bandinelli Stefania, Unnur Thorsteinsdottir, Michael Stumvoll, Jean-Claude Tardif, Elena Tremoli, Jaakko Tuomilehto, André G Uitterlinden, Matti Uusitupa, André L M Verbeek, Sita H Vermeulen, Jorma S Viikari, Veronique Vitart, Henry Völzke, Peter Vollenweider, Gérard Waeber, Mark Walker, Henri Wallaschofski, Nicholas J Wareham, Hugh Watkins, Eleftheria Zeggini, arcOGEN Consortium, CHARGE Consortium, DIAGRAM Consortium, GLGC Consortium, Global-BPGen Consortium, ICBP Consortium, MAGIC Consortium, Aravinda Chakravarti, Deborah J Clegg, L Adrienne Cupples, Penny Gordon-Larsen, Cashell E Jaquish, D C Rao, Goncalo R Abecasis, Themistocles L Assimes, Inês Barroso, Sonja I Berndt, Michael Boehnke, Panos Deloukas, Caroline S Fox, Leif C Groop, David J Hunter, Erik Ingelsson, Robert C Kaplan, Mark I McCarthy, Karen L Mohlke, Jeffrey R O'Connell, David Schlessinger, David P Strachan, Kari Stefansson, Cornelia M van Duijn, Joel N Hirschhorn, Cecilia M Lindgren, Iris M Heid, Kari E North, Ingrid B Borecki, Zoltán Kutalik, and Ruth J F Loos
Subjects: Genetics, QH426-470
Abstract: [This corrects the article DOI: 10.1371/journal.pgen.1005378.].
Published: 2016
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7. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.

Author: Thomas W Winkler, Anne E Justice, Mariaelisa Graff, Llilda Barata, Mary F Feitosa, Su Chu, Jacek Czajkowski, Tõnu Esko, Tove Fall, Tuomas O Kilpeläinen, Yingchang Lu, Reedik Mägi, Evelin Mihailov, Tune H Pers, Sina Rüeger, Alexander Teumer, Georg B Ehret, Teresa Ferreira, Nancy L Heard-Costa, Juha Karjalainen, Vasiliki Lagou, Anubha Mahajan, Michael D Neinast, Inga Prokopenko, Jeannette Simino, Tanya M Teslovich, Rick Jansen, Harm-Jan Westra, Charles C White, Devin Absher, Tarunveer S Ahluwalia, Shafqat Ahmad, Eva Albrecht, Alexessander Couto Alves, Jennifer L Bragg-Gresham, Anton J M de Craen, Joshua C Bis, Amélie Bonnefond, Gabrielle Boucher, Gemma Cadby, Yu-Ching Cheng, Charleston W K Chiang, Graciela Delgado, Ayse Demirkan, Nicole Dueker, Niina Eklund, Gudny Eiriksdottir, Joel Eriksson, Bjarke Feenstra, Krista Fischer, Francesca Frau, Tessel E Galesloot, Frank Geller, Anuj Goel, Mathias Gorski, Tanja B Grammer, Stefan Gustafsson, Saskia Haitjema, Jouke-Jan Hottenga, Jennifer E Huffman, Anne U Jackson, Kevin B Jacobs, Åsa Johansson, Marika Kaakinen, Marcus E Kleber, Jari Lahti, Irene Mateo Leach, Benjamin Lehne, Youfang Liu, Ken Sin Lo, Mattias Lorentzon, Jian'an Luan, Pamela A F Madden, Massimo Mangino, Barbara McKnight, Carolina Medina-Gomez, Keri L Monda, May E Montasser, Gabriele Müller, Martina Müller-Nurasyid, Ilja M Nolte, Kalliope Panoutsopoulou, Laura Pascoe, Lavinia Paternoster, Nigel W Rayner, Frida Renström, Federica Rizzi, Lynda M Rose, Kathy A Ryan, Perttu Salo, Serena Sanna, Hubert Scharnagl, Jianxin Shi, Albert Vernon Smith, Lorraine Southam, Alena Stančáková, Valgerdur Steinthorsdottir, Rona J Strawbridge, Yun Ju Sung, Ioanna Tachmazidou, Toshiko Tanaka, Gudmar Thorleifsson, Stella Trompet, Natalia Pervjakova, Jonathan P Tyrer, Liesbeth Vandenput, Sander W van der Laan, Nathalie van der Velde, Jessica van Setten, Jana V van Vliet-Ostaptchouk, Niek Verweij, Efthymia Vlachopoulou, Lindsay L Waite, Sophie R Wang, Zhaoming Wang, Sarah H Wild, Christina Willenborg, James F Wilson, Andrew Wong, Jian Yang, Loïc Yengo, Laura M Yerges-Armstrong, Lei Yu, Weihua Zhang, Jing Hua Zhao, Ehm A Andersson, Stephan J L Bakker, Damiano Baldassarre, Karina Banasik, Matteo Barcella, Cristina Barlassina, Claire Bellis, Paola Benaglio, John Blangero, Matthias Blüher, Fabrice Bonnet, Lori L Bonnycastle, Heather A Boyd, Marcel Bruinenberg, Aron S Buchman, Harry Campbell, Yii-Der Ida Chen, Peter S Chines, Simone Claudi-Boehm, John Cole, Francis S Collins, Eco J C de Geus, Lisette C P G M de Groot, Maria Dimitriou, Jubao Duan, Stefan Enroth, Elodie Eury, Aliki-Eleni Farmaki, Nita G Forouhi, Nele Friedrich, Pablo V Gejman, Bruna Gigante, Nicola Glorioso, Alan S Go, Omri Gottesman, Jürgen Gräßler, Harald Grallert, Niels Grarup, Yu-Mei Gu, Linda Broer, Annelies C Ham, Torben Hansen, Tamara B Harris, Catharina A Hartman, Maija Hassinen, Nicholas Hastie, Andrew T Hattersley, Andrew C Heath, Anjali K Henders, Dena Hernandez, Hans Hillege, Oddgeir Holmen, Kees G Hovingh, Jennie Hui, Lise L Husemoen, Nina Hutri-Kähönen, Pirro G Hysi, Thomas Illig, Philip L De Jager, Shapour Jalilzadeh, Torben Jørgensen, J Wouter Jukema, Markus Juonala, Stavroula Kanoni, Maria Karaleftheri, Kay Tee Khaw, Leena Kinnunen, Steven J Kittner, Wolfgang Koenig, Ivana Kolcic, Peter Kovacs, Nikolaj T Krarup, Wolfgang Kratzer, Janine Krüger, Diana Kuh, Meena Kumari, Theodosios Kyriakou, Claudia Langenberg, Lars Lannfelt, Chiara Lanzani, Vaneet Lotay, Lenore J Launer, Karin Leander, Jaana Lindström, Allan Linneberg, Yan-Ping Liu, Stéphane Lobbens, Robert Luben, Valeriya Lyssenko, Satu Männistö, Patrik K Magnusson, Wendy L McArdle, Cristina Menni, Sigrun Merger, Lili Milani, Grant W Montgomery, Andrew P Morris, Narisu Narisu, Mari Nelis, Ken K Ong, Aarno Palotie, Louis Pérusse, Irene Pichler, Maria G Pilia, Anneli Pouta, Myriam Rheinberger, Rasmus Ribel-Madsen, Marcus Richards, Kenneth M Rice, Treva K Rice, Carlo Rivolta, Veikko Salomaa, Alan R Sanders, Mark A Sarzynski, Salome Scholtens, Robert A Scott, William R Scott, Sylvain Sebert, Sebanti Sengupta, Bengt Sennblad, Thomas Seufferlein, Angela Silveira, P Eline Slagboom, Jan H Smit, Thomas H Sparsø, Kathleen Stirrups, Ronald P Stolk, Heather M Stringham, Morris A Swertz, Amy J Swift, Ann-Christine Syvänen, Sian-Tsung Tan, Barbara Thorand, Anke Tönjes, Angelo Tremblay, Emmanouil Tsafantakis, Peter J van der Most, Uwe Völker, Marie-Claude Vohl, Judith M Vonk, Melanie Waldenberger, Ryan W Walker, Roman Wennauer, Elisabeth Widén, Gonneke Willemsen, Tom Wilsgaard, Alan F Wright, M Carola Zillikens, Suzanne C van Dijk, Natasja M van Schoor, Folkert W Asselbergs, Paul I W de Bakker, Jacques S Beckmann, John Beilby, David A Bennett, Richard N Bergman, Sven Bergmann, Carsten A Böger, Bernhard O Boehm, Eric Boerwinkle, Dorret I Boomsma, Stefan R Bornstein, Erwin P Bottinger, Claude Bouchard, John C Chambers, Stephen J Chanock, Daniel I Chasman, Francesco Cucca, Daniele Cusi, George Dedoussis, Jeanette Erdmann, Johan G Eriksson, Denis A Evans, Ulf de Faire, Martin Farrall, Luigi Ferrucci, Ian Ford, Lude Franke, Paul W Franks, Philippe Froguel, Ron T Gansevoort, Christian Gieger, Henrik Grönberg, Vilmundur Gudnason, Ulf Gyllensten, Per Hall, Anders Hamsten, Pim van der Harst, Caroline Hayward, Markku Heliövaara, Christian Hengstenberg, Andrew A Hicks, Aroon Hingorani, Albert Hofman, Frank Hu, Heikki V Huikuri, Kristian Hveem, Alan L James, Joanne M Jordan, Antti Jula, Mika Kähönen, Eero Kajantie, Sekar Kathiresan, Lambertus A L M Kiemeney, Mika Kivimaki, Paul B Knekt, Heikki A Koistinen, Jaspal S Kooner, Seppo Koskinen, Johanna Kuusisto, Winfried Maerz, Nicholas G Martin, Markku Laakso, Timo A Lakka, Terho Lehtimäki, Guillaume Lettre, Douglas F Levinson, Lars Lind, Marja-Liisa Lokki, Pekka Mäntyselkä, Mads Melbye, Andres Metspalu, Braxton D Mitchell, Frans L Moll, Jeffrey C Murray, Arthur W Musk, Markku S Nieminen, Inger Njølstad, Claes Ohlsson, Albertine J Oldehinkel, Ben A Oostra, Lyle J Palmer, James S Pankow, Gerard Pasterkamp, Nancy L Pedersen, Oluf Pedersen, Brenda W Penninx, Markus Perola, Annette Peters, Ozren Polašek, Peter P Pramstaller, Bruce M Psaty, Lu Qi, Thomas Quertermous, Olli T Raitakari, Tuomo Rankinen, Rainer Rauramaa, Paul M Ridker, John D Rioux, Fernando Rivadeneira, Jerome I Rotter, Igor Rudan, Hester M den Ruijter, Juha Saltevo, Naveed Sattar, Heribert Schunkert, Peter E H Schwarz, Alan R Shuldiner, Juha Sinisalo, Harold Snieder, Thorkild I A Sørensen, Tim D Spector, Jan A Staessen, Bandinelli Stefania, Unnur Thorsteinsdottir, Michael Stumvoll, Jean-Claude Tardif, Elena Tremoli, Jaakko Tuomilehto, André G Uitterlinden, Matti Uusitupa, André L M Verbeek, Sita H Vermeulen, Jorma S Viikari, Veronique Vitart, Henry Völzke, Peter Vollenweider, Gérard Waeber, Mark Walker, Henri Wallaschofski, Nicholas J Wareham, Hugh Watkins, Eleftheria Zeggini, CHARGE Consortium, DIAGRAM Consortium, GLGC Consortium, Global-BPGen Consortium, ICBP Consortium, MAGIC Consortium, Aravinda Chakravarti, Deborah J Clegg, L Adrienne Cupples, Penny Gordon-Larsen, Cashell E Jaquish, D C Rao, Goncalo R Abecasis, Themistocles L Assimes, Inês Barroso, Sonja I Berndt, Michael Boehnke, Panos Deloukas, Caroline S Fox, Leif C Groop, David J Hunter, Erik Ingelsson, Robert C Kaplan, Mark I McCarthy, Karen L Mohlke, Jeffrey R O'Connell, David Schlessinger, David P Strachan, Kari Stefansson, Cornelia M van Duijn, Joel N Hirschhorn, Cecilia M Lindgren, Iris M Heid, Kari E North, Ingrid B Borecki, Zoltán Kutalik, and Ruth J F Loos
Subjects: Genetics, QH426-470
Abstract: Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR
Published: 2015
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8. Discovery and Fine-Mapping of Glycaemic and Obesity-Related Trait Loci Using High-Density Imputation.

Author: Momoko Horikoshi, Reedik Mӓgi, Martijn van de Bunt, Ida Surakka, Antti-Pekka Sarin, Anubha Mahajan, Letizia Marullo, Gudmar Thorleifsson, Sara Hӓgg, Jouke-Jan Hottenga, Claes Ladenvall, Janina S Ried, Thomas W Winkler, Sara M Willems, Natalia Pervjakova, Tõnu Esko, Marian Beekman, Christopher P Nelson, Christina Willenborg, Steven Wiltshire, Teresa Ferreira, Juan Fernandez, Kyle J Gaulton, Valgerdur Steinthorsdottir, Anders Hamsten, Patrik K E Magnusson, Gonneke Willemsen, Yuri Milaneschi, Neil R Robertson, Christopher J Groves, Amanda J Bennett, Terho Lehtimӓki, Jorma S Viikari, Johan Rung, Valeriya Lyssenko, Markus Perola, Iris M Heid, Christian Herder, Harald Grallert, Martina Müller-Nurasyid, Michael Roden, Elina Hypponen, Aaron Isaacs, Elisabeth M van Leeuwen, Lennart C Karssen, Evelin Mihailov, Jeanine J Houwing-Duistermaat, Anton J M de Craen, Joris Deelen, Aki S Havulinna, Matthew Blades, Christian Hengstenberg, Jeanette Erdmann, Heribert Schunkert, Jaakko Kaprio, Martin D Tobin, Nilesh J Samani, Lars Lind, Veikko Salomaa, Cecilia M Lindgren, P Eline Slagboom, Andres Metspalu, Cornelia M van Duijn, Johan G Eriksson, Annette Peters, Christian Gieger, Antti Jula, Leif Groop, Olli T Raitakari, Chris Power, Brenda W J H Penninx, Eco de Geus, Johannes H Smit, Dorret I Boomsma, Nancy L Pedersen, Erik Ingelsson, Unnur Thorsteinsdottir, Kari Stefansson, Samuli Ripatti, Inga Prokopenko, Mark I McCarthy, Andrew P Morris, and ENGAGE Consortium
Subjects: Genetics, QH426-470
Abstract: Reference panels from the 1000 Genomes (1000G) Project Consortium provide near complete coverage of common and low-frequency genetic variation with minor allele frequency ≥0.5% across European ancestry populations. Within the European Network for Genetic and Genomic Epidemiology (ENGAGE) Consortium, we have undertaken the first large-scale meta-analysis of genome-wide association studies (GWAS), supplemented by 1000G imputation, for four quantitative glycaemic and obesity-related traits, in up to 87,048 individuals of European ancestry. We identified two loci for body mass index (BMI) at genome-wide significance, and two for fasting glucose (FG), none of which has been previously reported in larger meta-analysis efforts to combine GWAS of European ancestry. Through conditional analysis, we also detected multiple distinct signals of association mapping to established loci for waist-hip ratio adjusted for BMI (RSPO3) and FG (GCK and G6PC2). The index variant for one association signal at the G6PC2 locus is a low-frequency coding allele, H177Y, which has recently been demonstrated to have a functional role in glucose regulation. Fine-mapping analyses revealed that the non-coding variants most likely to drive association signals at established and novel loci were enriched for overlap with enhancer elements, which for FG mapped to promoter and transcription factor binding sites in pancreatic islets, in particular. Our study demonstrates that 1000G imputation and genetic fine-mapping of common and low-frequency variant association signals at GWAS loci, integrated with genomic annotation in relevant tissues, can provide insight into the functional and regulatory mechanisms through which their effects on glycaemic and obesity-related traits are mediated.
Published: 2015
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9. Educational attainment influences levels of homozygosity through migration and assortative mating.

Author: Abdel Abdellaoui, Jouke-Jan Hottenga, Gonneke Willemsen, Meike Bartels, Toos van Beijsterveldt, Erik A Ehli, Gareth E Davies, Andrew Brooks, Patrick F Sullivan, Brenda W J H Penninx, Eco J de Geus, and Dorret I Boomsma
Subjects: Medicine, Science
Abstract: Individuals with a higher education are more likely to migrate, increasing the chance of meeting a spouse with a different ancestral background. In this context, the presence of strong educational assortment can result in greater ancestry differences within more educated spouse pairs, while less educated individuals are more likely to mate with someone with whom they share more ancestry. We examined the association between educational attainment and F roh (= the proportion of the genome consisting of runs of homozygosity [ROHs]) in ~2,000 subjects of Dutch ancestry. The subjects' own educational attainment showed a nominally significant negative association with F roh (p = .045), while the contribution of parental education to offspring F roh was highly significant (father: p < 10(-5); mother: p = 9 × 10(-5)), with more educated parents having offspring with fewer ROHs. This association was significantly and fully mediated by the physical distance between parental birthplaces (paternal education: pmediation = 2.4 × 10(-4); maternal education: pmediation = 2.3 × 10(-4)), which itself was also significantly associated with F roh (p = 9 × 10(-5)). Ancestry-informative principal components from the offspring showed a significantly decreasing association with geography as parental education increased, consistent with the significantly higher migration rates among more educated parents. Parental education also showed a high spouse correlation (Spearman's ρ = .66, p = 3 × 10(-262)). We show that less educated parents are less likely to mate with the more mobile parents with a higher education, creating systematic differences in homozygosity due to ancestry differences not directly captured by ancestry-informative principal components (PCs). Understanding how behaviors influence the genomic structure of a population is highly valuable for studies on the genetic etiology of behavioral, cognitive, and social traits.
Published: 2015
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10. Effect of genome and environment on metabolic and inflammatory profiles.

Author: Marina Sirota, Gonneke Willemsen, Purnima Sundar, Steven J Pitts, Shobha Potluri, Edi Prifti, Sean Kennedy, S Dusko Ehrlich, Jacoline Neuteboom, Cornelis Kluft, Karen E Malone, David R Cox, Eco J C de Geus, and Dorret I Boomsma
Subjects: Medicine, Science
Abstract: Twin and family studies have established the contribution of genetic factors to variation in metabolic, hematologic and immunological parameters. The majority of these studies analyzed single or combined traits into pre-defined syndromes. In the present study, we explore an alternative multivariate approach in which a broad range of metabolic, hematologic, and immunological traits are analyzed simultaneously to determine the resemblance of monozygotic (MZ) twin pairs, twin-spouse pairs and unrelated, non-cohabiting individuals. A total of 517 participants from the Netherlands Twin Register, including 210 MZ twin pairs and 64 twin-spouse pairs, took part in the study. Data were collected on body composition, blood pressure, heart rate, and multiple biomarkers assessed in fasting blood samples, including lipid levels, glucose, insulin, liver enzymes, hematological measurements and cytokine levels. For all 51 measured traits, pair-wise Pearson correlations, correcting for family relatedness, were calculated across all the individuals in the cohort. Hierarchical clustering techniques were applied to group the measured traits into sub-clusters based on similarity. Sub-clusters were observed among metabolic traits and among inflammatory markers. We defined a phenotypic profile as the collection of all the traits measured for a given individual. Average within-pair similarity of phenotypic profiles was determined for the groups of MZ twin pairs, spouse pairs and pairs of unrelated individuals. The average similarity across the full phenotypic profile was higher for MZ twin pairs than for spouse pairs, and lowest for pairs of unrelated individuals. Cohabiting MZ twins were more similar in their phenotypic profile compared to MZ twins who no longer lived together. The correspondence in the phenotypic profile is therefore determined to a large degree by familial, mostly genetic, factors, while household factors contribute to a lesser degree to profile similarity.
Published: 2015
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11. Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers.

Author: Amy E Taylor, Richard W Morris, Meg E Fluharty, Johan H Bjorngaard, Bjørn Olav Åsvold, Maiken E Gabrielsen, Archie Campbell, Riccardo Marioni, Meena Kumari, Jenni Hällfors, Satu Männistö, Pedro Marques-Vidal, Marika Kaakinen, Alana Cavadino, Iris Postmus, Lise Lotte N Husemoen, Tea Skaaby, Tarunveer S Ahluwalia, Jorien L Treur, Gonneke Willemsen, Caroline Dale, S Goya Wannamethee, Jari Lahti, Aarno Palotie, Katri Räikkönen, Aliaksei Kisialiou, Alex McConnachie, Sandosh Padmanabhan, Andrew Wong, Christine Dalgård, Lavinia Paternoster, Yoav Ben-Shlomo, Jessica Tyrrell, John Horwood, David M Fergusson, Martin A Kennedy, Tim Frayling, Ellen A Nohr, Lene Christiansen, Kirsten Ohm Kyvik, Diana Kuh, Graham Watt, Johan Eriksson, Peter H Whincup, Jacqueline M Vink, Dorret I Boomsma, George Davey Smith, Debbie Lawlor, Allan Linneberg, Ian Ford, J Wouter Jukema, Christine Power, Elina Hyppönen, Marjo-Riitta Jarvelin, Martin Preisig, Katja Borodulin, Jaakko Kaprio, Mika Kivimaki, Blair H Smith, Caroline Hayward, Pål R Romundstad, Thorkild I A Sørensen, Marcus R Munafò, and Naveed Sattar
Subjects: Genetics, QH426-470
Abstract: We previously used a single nucleotide polymorphism (SNP) in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI) in a Mendelian randomisation analysis. While seeking to extend these findings in a larger sample we found that this SNP is associated with 0.74% lower body mass index (BMI) per minor allele in current smokers (95% CI -0.97 to -0.51, P = 2.00 × 10(-10)), but also unexpectedly found that it was associated with 0.35% higher BMI in never smokers (95% CI +0.18 to +0.52, P = 6.38 × 10(-5)). An interaction test confirmed that these estimates differed from each other (P = 4.95 × 10(-13)). This difference in effects suggests the variant influences BMI both via pathways unrelated to smoking, and via the weight-reducing effects of smoking. It would therefore be essentially undetectable in an unstratified genome-wide association study of BMI, given the opposite association with BMI in never and current smokers. This demonstrates that novel associations may be obscured by hidden population sub-structure. Stratification on well-characterized environmental factors known to impact on health outcomes may therefore reveal novel genetic associations.
Published: 2014
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12. No evidence for genome-wide interactions on plasma fibrinogen by smoking, alcohol consumption and body mass index: results from meta-analyses of 80,607 subjects.

Author: Jens Baumert, Jie Huang, Barbara McKnight, Maria Sabater-Lleal, Maristella Steri, Audrey Y Chu, Stella Trompet, Lorna M Lopez, Myriam Fornage, Alexander Teumer, Weihong Tang, Alicja R Rudnicka, Anders Mälarstig, Jouke-Jan Hottenga, Maryam Kavousi, Jari Lahti, Toshiko Tanaka, Caroline Hayward, Jennifer E Huffman, Pierre-Emmanuel Morange, Lynda M Rose, Saonli Basu, Ann Rumley, David J Stott, Brendan M Buckley, Anton J M de Craen, Serena Sanna, Marco Masala, Reiner Biffar, Georg Homuth, Angela Silveira, Bengt Sennblad, Anuj Goel, Hugh Watkins, Martina Müller-Nurasyid, Regina Rückerl, Kent Taylor, Ming-Huei Chen, Eco J C de Geus, Albert Hofman, Jacqueline C M Witteman, Moniek P M de Maat, Aarno Palotie, Gail Davies, David S Siscovick, Ivana Kolcic, Sarah H Wild, Jaejoon Song, Wendy L McArdle, Ian Ford, Naveed Sattar, David Schlessinger, Anne Grotevendt, Maria Grazia Franzosi, Thomas Illig, Melanie Waldenberger, Thomas Lumley, Geoffrey H Tofler, Gonneke Willemsen, André G Uitterlinden, Fernando Rivadeneira, Katri Räikkönen, Daniel I Chasman, Aaron R Folsom, Gordon D Lowe, Rudi G J Westendorp, P Eline Slagboom, Francesco Cucca, Henri Wallaschofski, Rona J Strawbridge, Udo Seedorf, Wolfgang Koenig, Joshua C Bis, Kenneth J Mukamal, Jenny van Dongen, Elisabeth Widen, Oscar H Franco, John M Starr, Kiang Liu, Luigi Ferrucci, Ozren Polasek, James F Wilson, Tiphaine Oudot-Mellakh, Harry Campbell, Pau Navarro, Stefania Bandinelli, Johan Eriksson, Dorret I Boomsma, Abbas Dehghan, Robert Clarke, Anders Hamsten, Eric Boerwinkle, J Wouter Jukema, Silvia Naitza, Paul M Ridker, Henry Völzke, Ian J Deary, Alexander P Reiner, David-Alexandre Trégouët, Christopher J O'Donnell, David P Strachan, Annette Peters, and Nicholas L Smith
Subjects: Medicine, Science
Abstract: Plasma fibrinogen is an acute phase protein playing an important role in the blood coagulation cascade having strong associations with smoking, alcohol consumption and body mass index (BMI). Genome-wide association studies (GWAS) have identified a variety of gene regions associated with elevated plasma fibrinogen concentrations. However, little is yet known about how associations between environmental factors and fibrinogen might be modified by genetic variation. Therefore, we conducted large-scale meta-analyses of genome-wide interaction studies to identify possible interactions of genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentration. The present study included 80,607 subjects of European ancestry from 22 studies. Genome-wide interaction analyses were performed separately in each study for about 2.6 million single nucleotide polymorphisms (SNPs) across the 22 autosomal chromosomes. For each SNP and risk factor, we performed a linear regression under an additive genetic model including an interaction term between SNP and risk factor. Interaction estimates were meta-analysed using a fixed-effects model. No genome-wide significant interaction with smoking status, alcohol consumption or BMI was observed in the meta-analyses. The most suggestive interaction was found for smoking and rs10519203, located in the LOC123688 region on chromosome 15, with a p value of 6.2 × 10(-8). This large genome-wide interaction study including 80,607 participants found no strong evidence of interaction between genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentrations. Further studies are needed to yield deeper insight in the interplay between environmental factors and gene variants on the regulation of fibrinogen concentrations.
Published: 2014
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13. Identifying genetic variants for heart rate variability in the acetylcholine pathway.

Author: Harriëtte Riese, Loretto M Muñoz, Catharina A Hartman, Xiuhua Ding, Shaoyong Su, Albertine J Oldehinkel, Arie M van Roon, Peter J van der Most, Joop Lefrandt, Ron T Gansevoort, Pim van der Harst, Niek Verweij, Carmilla M M Licht, Dorret I Boomsma, Jouke-Jan Hottenga, Gonneke Willemsen, Brenda W J H Penninx, Ilja M Nolte, Eco J C de Geus, Xiaoling Wang, and Harold Snieder
Subjects: Medicine, Science
Abstract: Heart rate variability is an important risk factor for cardiovascular disease and all-cause mortality. The acetylcholine pathway plays a key role in explaining heart rate variability in humans. We assessed whether 443 genotyped and imputed common genetic variants in eight key genes (CHAT, SLC18A3, SLC5A7, CHRNB4, CHRNA3, CHRNA, CHRM2 and ACHE) of the acetylcholine pathway were associated with variation in an established measure of heart rate variability reflecting parasympathetic control of the heart rhythm, the root mean square of successive differences (RMSSD) of normal RR intervals. The association was studied in a two stage design in individuals of European descent. First, analyses were performed in a discovery sample of four cohorts (n = 3429, discovery stage). Second, findings were replicated in three independent cohorts (n = 3311, replication stage), and finally the two stages were combined in a meta-analysis (n = 6740). RMSSD data were obtained under resting conditions. After correction for multiple testing, none of the SNPs showed an association with RMSSD. In conclusion, no common genetic variants for heart rate variability were identified in the largest and most comprehensive candidate gene study on the acetylcholine pathway to date. Future gene finding efforts for RMSSD may want to focus on hypothesis free approaches such as the genome-wide association study.
Published: 2014
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14. Correction: DeepSAGE Reveals Genetic Variants Associated with Alternative Polyadenylation and Expression of Coding and Non-coding Transcripts.

Author: Daria V. Zhernakova, Eleonora de Klerk, Harm-Jan Westra, Anastasios Mastrokolias, Shoaib Amini, Yavuz Ariyurek, Rick Jansen, Brenda W. Penninx, Jouke J. Hottenga, Gonneke Willemsen, Eco J. de Geus, Dorret I. Boomsma, Jan H. Veldink, Leonard H. van den Berg, Cisca Wijmenga, Johan T. den Dunnen, Gert-Jan B. van Ommen, Peter A. C. 't Hoen, and Lude Franke
Subjects: Genetics, QH426-470
Published: 2013
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15. DeepSAGE reveals genetic variants associated with alternative polyadenylation and expression of coding and non-coding transcripts.

Author: Daria V Zhernakova, Eleonora de Klerk, Harm-Jan Westra, Anastasios Mastrokolias, Shoaib Amini, Yavuz Ariyurek, Rick Jansen, Brenda W Penninx, Jouke J Hottenga, Gonneke Willemsen, Eco J de Geus, Dorret I Boomsma, Jan H Veldink, Leonard H van den Berg, Cisca Wijmenga, Johan T den Dunnen, Gert-Jan B van Ommen, Peter A C 't Hoen, and Lude Franke
Subjects: Genetics, QH426-470
Abstract: Many disease-associated variants affect gene expression levels (expression quantitative trait loci, eQTLs) and expression profiling using next generation sequencing (NGS) technology is a powerful way to detect these eQTLs. We analyzed 94 total blood samples from healthy volunteers with DeepSAGE to gain specific insight into how genetic variants affect the expression of genes and lengths of 3'-untranslated regions (3'-UTRs). We detected previously unknown cis-eQTL effects for GWAS hits in disease- and physiology-associated traits. Apart from cis-eQTLs that are typically easily identifiable using microarrays or RNA-sequencing, DeepSAGE also revealed many cis-eQTLs for antisense and other non-coding transcripts, often in genomic regions containing retrotransposon-derived elements. We also identified and confirmed SNPs that affect the usage of alternative polyadenylation sites, thereby potentially influencing the stability of messenger RNAs (mRNA). We then combined the power of RNA-sequencing with DeepSAGE by performing a meta-analysis of three datasets, leading to the identification of many more cis-eQTLs. Our results indicate that DeepSAGE data is useful for eQTL mapping of known and unknown transcripts, and for identifying SNPs that affect alternative polyadenylation. Because of the inherent differences between DeepSAGE and RNA-sequencing, our complementary, integrative approach leads to greater insight into the molecular consequences of many disease-associated variants.
Published: 2013
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16. 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
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17. 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
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18. 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
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19. 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
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20. 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
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21. 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
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22. 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
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23. 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
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24. 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
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25. 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
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26. 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
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27. 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
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28. Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults

Author: Amélie Bonnefond, Nancy L. Heard-Costa, Julius S. Ngwa, Jennifer E. Huffman, Tanja B. Grammer, Jaakko Tuomilehto, Lu Qi, Nicholas G. Martin, Massimo Mangino, Henrik Vestergaard, Penny Gordon-Larsen, Reedik Mägi, Natalia V. Rivera, Charles Kooperberg, Alain G. Bertoni, Sarah H. Wild, Robert Luben, Veikko Salomaa, Claude Bouchard, Lynda M. Rose, Patricia A. Peyser, Graciela E. Delgado, Jessica D. Faul, Tuija Tammelin, John C. Chambers, Tsegaselassie Workalemahu, Kari E. North, David J. Porteous, Peter Vollenweider, Kennet Harald, Claire Bellis, Serena Sanna, Nicholas D. Hastie, Robert J. Klein, Marie-Claude Vohl, Ruth J. F. Loos, Jian Gong, Igor Rudan, Unhee Lim, Christopher A. Haiman, Martina Müller-Nurasyid, Konstantin Strauch, Mark A. Sarzynski, Albert V. Smith, Mark Walker, Tapani Ebeling, Göran Hallmans, Nicole Dueker, Caroline S. Fox, Sven Bergmann, Keri L. Monda, Thorkild I. A. Sørensen, André G. Uitterlinden, Johanne Marie Justesen, Aki S. Havulinna, Torben Hansen, Ivana Kolcic, Cecilia M. Lindgren, Marcel den Hoed, Richard N. Bergman, Mariaelisa Graff, Alan R. Shuldiner, Dorota Pasko, James F. Wilson, John Whitfield, Joel Eriksson, Jaspal S. Kooner, Mette Hollensted, Winfried März, Gonçalo R. Abecasis, Weihua Zhang, Harold Snieder, Rajesh Rawal, Tao Huang, Åsa Johansson, Lydia Quaye, Ying Wu, Benjamin Lehne, Matthias Nauck, Caroline Hayward, Linda S. Adair, Michel Marre, Tanguy Corre, Alan James, Frida Renström, Jian'an Luan, Zoltán Kutalik, Kurt Lohman, Jennifer A. Smith, Mao Fu, Jennifer L. Bragg-Gresham, Tamara B. Harris, Claudia Langenberg, Tõnu Esko, Mattias Lorentzon, Ken K. Ong, Blair H. Smith, Fabio Busonero, Alan F. Wright, Gemma Cadby, Andrew D. Johnson, Steve Buyske, Anubha Mahajan, Antonella Mulas, Gérard Waeber, Lori L. Bonnycastle, Daniel I. Chasman, Jennie Hui, Audrey Y. Chu, Uwe Völker, Albertine J. Oldehinkel, Jing Hua Zhao, Robert A. Scott, Ilja M. Nolte, Loic LeMarchand, Yu-Ching Cheng, David P. Strachan, Jie Huang, Gerard van Grootheest, John D. Eicher, Marcus E. Kleber, Francis S. Collins, Cornelia M. van Duijn, Timothy M. Frayling, Pau Navarro, Leo-Pekka Lyytikäinen, Cinzia Sarti, Paul M. Ridker, John-Olov Jansson, Shafqat Ahmad, Philippe Froguel, Albert Hofman, Inga Prokopenko, Vilmundur Gudnason, Anne U. Jackson, David R. Weir, Lyle J. Palmer, Alexander Teumer, Ulf Gyllensten, Mette Aadahl, Niels Grarup, Beverley Balkau, Oluf Pedersen, Cornelia Huth, Dorret I. Boomsma, Harry Campbell, Charlotte Huppertz, Ingrid B. Borecki, Juha Auvinen, Soren Snitker, Yuri Milaneschi, Iris M. Heid, Barbara Thorand, Wouter J. Peyrot, Lavinia Paternoster, Sian-Tsung Tan, Anne E. Justice, Dena G. Hernandez, Marcus Dörr, Nicholas J. Wareham, Marilyn C. Cornelis, Claes Ohlsson, Amy J. Swift, Ozren Polasek, Brenda W.J.H. Penninx, James E. Hayes, Stephanie A. Bien, Jana V. van Vliet-Ostaptchouk, Eric Boerwinkle, Louis Pérusse, Peter J. van der Most, Ulrike Peters, Pirjo Komulainen, Lynne J. Hocking, Catharina A. Hartman, William R. Scott, Jeffrey R. O'Connell, Stefania Bandinelli, Tuomo Rankinen, Timo A. Lakka, Leena Kinnunen, Markus Perola, John Blangero, Sharon L.R. Kardia, Veronique Vitart, Mika Kähönen, Marie Neergaard Harder, Diana Kuh, Kai Savonen, Kristin L. Young, Jeremiah Perez, Nina Hutri-Kähönen, George Davey Smith, Toshiko Tanaka, Barbara Sternfeld, Jennifer A. Nettleton, Jouke-Jan Hottenga, Christian Gieger, Gonneke Willemsen, Soren Brage, Mika Kivimäki, Lucia A. Hindorff, Steve Sidney, Tarunveer S. Ahluwalia, Liesbeth Vandenput, Loic Yengo, Markku Laakso, Yongmei Liu, Arthur W. Musk, Harald Grallert, Kirsti Kvaløy, Rainer Rauramaa, Satu Männistö, Tuomas O. Kilpeläinen, M. Carola Zillikens, Hannu Puolijoki, Luting Xue, Oddgeir L. Holmens, Sandosh Padmanabhan, Inês Barroso, Ching-Ti Liu, L. Adrienne Cupples, Judith B. Borja, Karen L. Mohlke, Matthias Olden, Henry Völzke, Myriam Fornage, Michael Boehnke, Pedro Marques-Vidal, John Beilby, Fernando Rivadeneira, Maija Hassinen, Najaf Amin, Kristian Hveem, Gudny Eiriksdottir, Lenore J. Launer, Johanna Kuusisto, Dorothée Thuillier, Heather M. Stringham, Sven Gläser, Min A. Jhun, Marjo-Riitta Järvelin, Niha Zubair, Annette Peters, Llilda Barata, Paula J. Griffin, Markus Juonala, Wei Zhao, Andres Metspalu, Christina Holzapfel, Lawrence F. Bielak, Thomas W. Winkler, Alena Stančáková, Anke Tönjes, Narisu Narisu, David Hadley, Peter S. Chines, Andrew Wong, Günther Silbernagel, Kati Kristiansson, Eco J. C. de Geus, Grant W. Montgomery, Elise Lim, Laura J. Rasmussen-Torvik, Terho Lehtimäki, Heikki A. Koistinen, Meena Kumari, Qibin Qi, Ayse Demirkan, Francesco Cucca, Allan Linneberg, Reija Männikkö, Jonathan Marten, Olli T. Raitakari, Mary F. Feitosa, Paul W. Franks, Kristine Færch, Mark I. McCarthy, Marleen H.M. de Moor, Joel N. Hirschhorn, Toomas Haller, Graff, Mariaelisa [0000-0001-6380-1735], Young, Kristin L [0000-0003-0070-6145], Winkler, Thomas W [0000-0003-0292-5421], Heard-Costa, Nancy L [0000-0001-9730-0306], Renström, Frida [0000-0001-6053-298X], Barroso, Inês [0000-0001-5800-4520], Strachan, David P [0000-0001-7854-1366], Liu, Ching-Ti [0000-0002-0703-0742], Klein, Robert J [0000-0003-3539-5391], Apollo - University of Cambridge Repository, University of Helsinki, Institute for Molecular Medicine Finland, Quantitative Genetics, Clinicum, Department of Medicine, Endokrinologian yksikkö, HUS Internal Medicine and Rehabilitation, Complex Disease Genetics, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, CHARGE Consortium, EPIC-InterAct Consortium, PAGE Consortium, Edwards, Todd L., Biological Psychology, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Clinical Child and Family Studies, APH - Methodology, School of Medicine / Biomedicine, Public and occupational health, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, APH - Digital Health, Life Course Epidemiology (LCE), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Center for Liver, Digestive and Metabolic Diseases (CLDM), Epidemiology, Medical Microbiology & Infectious Diseases, Erasmus MC other, Child and Adolescent Psychiatry / Psychology, and Internal Medicine
Subjects: Netherlands Twin Register (NTR), Epigenomics, Male, Genome-wide association study, genome, obesity, BMI, Body Mass Index, 0302 clinical medicine, Cell Signaling, Public and Occupational Health, GENE-EXPRESSION, Adiposity, Genetics & Heredity, ADIPOCYTE DIFFERENTIATION, 1184 Genetics, developmental biology, physiology, Genomics, Functional Genomics, 3. Good health, Meta-analysis, Physical Sciences, REACTIVE PROTEIN-LEVELS, Waist Circumference, Statistics (Mathematics), Waist, Genotype, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Single-nucleotide polymorphism, Locus (genetics), BINDING PROTEIN, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Genome-Wide Association Studies, Genetics, Humans, Statistical Methods, Molecular Biology, Exercise, Ecology, Evolution, Behavior and Systematics, 0604 Genetics, Science & Technology, ASSOCIATION METAANALYSIS, Physical activity, ta1184, Biology and Life Sciences, Computational Biology, Physical Activity, 030104 developmental biology, Genetic Loci, Body mass index, Mathematics, 030217 neurology & neurosurgery, Meta-Analysis, Developmental Biology, BODY-MASS INDEX, IDENTICAL-TWINS, ACTIVITY QUESTIONNAIRES, FAT DISTRIBUTION, FOOD-INTAKE, 0301 basic medicine, Cancer Research, Medicin och hälsovetenskap, Offita, Physiology, FTO gene, Genome-wide association studies, Medical and Health Sciences, Mathematical and Statistical Techniques, Waist–hip ratio, Medicine and Health Sciences, Genetics (clinical), Public Health, Global Health, Social Medicine and Epidemiology, Physiological Parameters, Female, Genomic Signal Processing, Life Sciences & Biomedicine, Research Article, Signal Transduction, lcsh:QH426-470, Biology, Research and Analysis Methods, Hreyfing (heilsurækt), Journal Article, Erfðafræði, Genetic Predisposition to Disease, Obesity, Waist-Hip Ratio, Body Weight, Human Genetics, Cell Biology, Rannsóknir, Genome Analysis, lcsh:Genetics, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, 3111 Biomedicine, Genome-Wide Association Study
Abstract: Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery., The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. Funding for this study was provided by the Aase and Ejner Danielsens Foundation; Academy of Finland (102318; 104781, 120315, 123885, 129619, 286284, 134309, 126925, 121584, 124282, 129378, 117787, 250207, 258753, 41071, 77299, 124243, 1114194, 24300796); Accare Center for Child and Adolescent Psychiatry; Action on Hearing Loss (G51); Agence Nationale de la Recherche; Agency for Health Care Policy Research (HS06516); Age UK Research into Ageing Fund; Åke Wiberg Foundation; ALF/LUA Research Grant in Gothenburg; ALFEDIAM; ALK-Abello´ A/S (Hørsholm, Denmark); American Heart Association (13POST16500011, 10SDG269004); Ardix Medical; Arthritis Research UK; Association Diabète Risque Vasculaire; AstraZeneca; Australian Associated Brewers; Australian National Health and Medical Research Council (241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498); Avera Research Institute; Bayer Diagnostics; Becton Dickinson; Biobanking and Biomolecular Resources Research Infrastructure (BBMRI –NL, 184.021.007); Biocentrum Helsinki; Boston Obesity Nutrition Research Center (DK46200); British Heart Foundation (RG/10/12/28456, SP/04/002); Canada Foundation for Innovation; Canadian Institutes of Health Research (FRN-CCT-83028); Cancer Research UK; Cardionics; Center for Medical Systems Biology; Center of Excellence in Complex Disease Genetics and SALVECenter of Excellence in Genomics (EXCEGEN); Chief Scientist Office of the Scottish Government; City of Kuopio; Cohortes Santé TGIR; Contrat de Projets État-Région; Croatian Science Foundation (8875); Danish Agency for Science, Technology and Innovation; Danish Council for Independent Research (DFF–1333-00124, DFF–1331-007308); Danish Diabetes Academy; Danish Medical Research Council; Department of Psychology and Education of the VU University Amsterdam; Diabetes Hilfs- und Forschungsfonds Deutschland; Dutch Brain Foundation; Dutch Ministry of Justice; Emil Aaltonen Foundation; Erasmus Medical Center; Erasmus University; Estonian Government (IUT20-60, IUT24-6); Estonian Ministry of Education and Research (3.2.0304.11-0312); European Commission (230374, 284167, 323195, 692145, FP7 EurHEALTHAgeing-277849, FP7 BBMRI-LPC 313010, nr 602633, HEALTH-F2-2008-201865-GEFOS, HEALTH-F4-2007-201413, FP6 LSHM-CT-2004-005272, FP5 QLG2-CT-2002-01254, FP6 LSHG-CT-2006-01947, FP7 HEALTH-F4-2007-201413, FP7 279143, FP7 201668, FP7 305739, FP6 LSHG-CT-2006-018947, HEALTH-F4-2007-201413, QLG1-CT-2001-01252); European Regional Development Fund; European Science Foundation (EuroSTRESS project FP-006, ESF, EU/QLRT-2001-01254); Faculty of Biology and Medicine of Lausanne; Federal Ministry of Education and Research (01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012, 03IS2061A); Federal State of Mecklenburg - West Pomerania; Fédération Française de Cardiologie; Finnish Cultural Foundation; Finnish Diabetes Association; Finnish Foundation of Cardiovascular Research; Finnish Heart Association; Food Standards Agency; Fondation de France; Fonds Santé; Genetic Association Information Network of the Foundation for the National Institutes of Health; German Diabetes Association; German Federal Ministry of Education and Research (BMBF, 01ER1206, 01ER1507); German Research Council (SFB-1052, SPP 1629 TO 718/2-1); GlaxoSmithKline; Göran Gustafssons Foundation; Göteborg Medical Society; Health and Safety Executive; Heart Foundation of Northern Sweden; Icelandic Heart Association; Icelandic Parliament; Imperial College Healthcare NHS Trust; INSERM, Réseaux en Santé Publique, Interactions entre les déterminants de la santé; Interreg IV Oberrhein Program (A28); Italian Ministry of Economy and Finance; Italian Ministry of Health (ICS110.1/RF97.71); John D and Catherine T MacArthur Foundation; Juho Vainio Foundation; King's College London; Kjell och Märta Beijers Foundation; Kuopio University Hospital; Kuopio, Tampere and Turku University Hospital Medical Funds (X51001); Leiden University Medical Center; Lilly; LMUinnovativ; Lundbeck Foundation; Lundberg Foundation; Medical Research Council of Canada; MEKOS Laboratories (Denmark); Merck Santé; Mid-Atlantic Nutrition Obesity Research Center (P30 DK72488); Ministère de l’Économie, de l’Innovation et des Exportations; Ministry for Health, Welfare and Sports of the Netherlands; Ministry of Cultural Affairs of the Federal State of Mecklenburg-West Pomerania; Ministry of Education and Culture of Finland (627;2004-2011); Ministry of Education, Culture and Science of the Netherlands; MRC Human Genetics Unit; MRC-GlaxoSmithKline Pilot Programme Grant (G0701863); Municipality of Rotterdam; Netherlands Bioinformatics Centre (2008.024); Netherlands Consortium for Healthy Aging (050-060-810); Netherlands Genomics Initiative; Netherlands Organisation for Health Research and Development (904-61-090, 985-10-002, 904-61-193, 480-04-004, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192); Netherlands Organisation for Health Research and Development (2010/31471/ZONMW); Netherlands Organisation for Scientific Research (10-000-1002, GB-MW 940-38-011, 100-001-004, 60-60600-97-118, 261-98-710, GB-MaGW 480-01-006, GB-MaGW 480-07-001, GB-MaGW 452-04-314, GB-MaGW 452-06-004, 175.010.2003.005, 175.010.2005.011, 481-08-013, 480-05-003, 911-03-012); Neuroscience Campus Amsterdam; NHS Foundation Trust; Novartis Pharmaceuticals; Novo Nordisk; Office National Interprofessionel des Vins; Paavo Nurmi Foundation; Påhlssons Foundation; Päivikki and Sakari Sohlberg Foundation; Pierre Fabre; Republic of Croatia Ministry of Science, Education and Sport (108-1080315-0302); Research Centre for Prevention and Health, the Capital Region for Denmark; Research Institute for Diseases in the Elderly (014-93-015, RIDE2); Roche; Russian Foundation for Basic Research (NWO-RFBR 047.017.043); Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06); Sanofi-Aventis; Scottish Executive Health Department (CZD/16/6); Siemens Healthcare; Social Insurance Institution of Finland (4/26/2010); Social Ministry of the Federal State of Mecklenburg-West Pomerania; Société Francophone du Diabète; State of Bavaria; Stroke Association; Swedish Diabetes Association; Swedish Foundation for Strategic Research; Swedish Heart-Lung Foundation (20140543); Swedish Research Council (2015-03657); Swedish Medical Research Council (K2007-66X-20270-01-3, 2011-2354); Swedish Society for Medical Research; Swiss National Science Foundation (33CSCO-122661, 33CS30-139468, 33CS30-148401); Tampere Tuberculosis Foundation; The Marcus Borgström Foundation; The Royal Society; The Wellcome Trust (084723/Z/08/Z, 088869/B/09/Z); Timber Merchant Vilhelm Bangs Foundation; Topcon; Torsten and Ragnar Söderberg's Foundation; UK Department of Health; UK Diabetes Association; UK Medical Research Council (MC_U106179471, G0500539, G0600705, G0601966, G0700931, G1002319, K013351, MC_UU_12019/1); UK National Institute for Health Research BioResource Clinical Research Facility and Biomedical Research Centre; UK National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre; UK National Institute for Health Research (RP-PG-0407-10371); Umeå University Career Development Award; United States – Israel Binational Science Foundation Grant (2011036); University Hospital Oulu (75617); University Medical Center Groningen; University of Tartu (SP1GVARENG); National Institutes of Health (AG13196, CA047988, HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSC271201100004C, HHSN268200900041C, HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN268201300028C, HHSN268201300029C, HHSN268201500001I, HL36310, HG002651, HL034594, HL054457, HL054481, HL071981, HL084729, HL119443, HL126024, N01-AG12100, N01-AG12109, N01-HC25195, N01-HC55015, N01-HC55016, N01-HC55018, N01-HC55019, N01-HC55020, N01-HC55021, N01-HC55022, N01-HD95159, N01-HD95160, N01-HD95161, N01-HD95162, N01-HD95163, N01-HD95164, N01-HD95165, N01-HD95166, N01-HD95167, N01-HD95168, N01-HD95169, N01-HG65403, N02-HL64278, R01-HD057194, R01-HL087641, R01-HL59367, R01HL-086694, R01-HL088451, R24-HD050924, U01-HG-004402, HHSN268200625226C, UL1-RR025005, UL1-RR025005, UL1-TR-001079, UL1-TR-00040, AA07535, AA10248, AA11998, AA13320, AA13321, AA13326, AA14041, AA17688, DA12854, MH081802, MH66206, R01-D004215701A, R01-DK075787, R01-DK089256, R01-DK8925601, R01-HL088451, R01-HL117078, R01-DK062370, R01-DK072193, DK091718, DK100383, DK078616, 1Z01-HG000024, HL087660, HL100245, R01DK089256, 2T32HL007055-36, U01-HL072515-06, U01-HL84756, NIA-U01AG009740, RC2-AG036495, RC4-AG039029, R03 AG046389, 263-MA-410953, 263-MD-9164, 263-MD-821336, U01-HG004802, R37CA54281, R01CA63, P01CA33619, U01-CA136792, U01-CA98758, RC2-MH089951, MH085520, R01-D0042157-01A, MH081802, 1RC2-MH089951, 1RC2-MH089995, 1RL1MH08326801, U01-HG007376, 5R01-HL08767902, 5R01MH63706:02, HG004790, N01-WH22110, U01-HG007033, UM1CA182913, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221); USDA National Institute of Food and Agriculture (2007-35205-17883); Västra Götaland Foundation; Velux Foundation; Veterans Affairs (1 IK2 BX001823); Vleugels Foundation; VU University’s Institute for Health and Care Research (EMGO+, HEALTH-F4-2007-201413) and Neuroscience Campus Amsterdam; Wellcome Trust (090532, 091551, 098051, 098381); Wissenschaftsoffensive TMO; and Yrjö Jahnsson Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Published: 2017
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29. Correction: 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: Multidisciplinary, Science, Correction, Medicine
Published: 2012

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

Author: Yvonne T. van der Schouw, Marten H. Hofker, Florianne Bauer, Cisca Wijmenga, Leen M 't Hart, Gonneke Willemsen, Jana V. van Vliet-Ostaptchouk, Elisabeth M. W. Eekhoff, Anthonius de Boer, Clara C. Elbers, Gijs W. D. Landman, Mark H. H. Kramer, Annemieke M.W. Spijkerman, Erwin Reiling, Dorret I. Boomsma, Hata Zavrelova, L.M.C. Welschen, Diederick E. Grobbee, Olaf H. Klungel, P. Eline Slagboom, Daphne L. van der A, Nanne Kleefstra, Cleo C. van Diemen, Michaela Diamant, E. J. Bruin, Jacqueline M. Dekker, Giel Nijpels, Henk J. G. Bilo, A.M.C. Simonis-Bik, N. Charlotte Onland-Moret, Esther van 't Riet, Eco J. C. de Geus, H. Marike Boezen, Timon W. van Haeften, Lifestyle Medicine (LM), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Groningen Research Institute for Asthma and COPD (GRIAC), Center for Liver, Digestive and Metabolic Diseases (CLDM), Vascular Ageing Programme (VAP), Epidemiology and Data Science, General practice, Ophthalmology, Internal medicine, ICaR - Heartfailure and pulmonary arterial hypertension, EMGO - Lifestyle, overweight and diabetes, Biological Psychology, and EMGO+ - Lifestyle, Overweight and Diabetes
Subjects: Male, Netherlands Twin Register (NTR), Heredity, Epidemiology, medicine.medical_treatment, lcsh:Medicine, Type 2 diabetes, THERAPY, chemistry.chemical_compound, MELLITUS, Endocrinology, DESIGN, Insulin Secretion, Insulin, lcsh:Science, Multidisciplinary, CHINESE HAN POPULATION, Middle Aged, Glucose clamp technique, KCNQ1 Potassium Channel, Medicine, Female, Research Article, medicine.medical_specialty, SUSCEPTIBILITY LOCI, NEPHROPATHY, Polymorphism, Single Nucleotide, Nephropathy, Diabetes Complications, BETA-CELL FUNCTION, SDG 3 - Good Health and Well-being, Internal medicine, Diabetes mellitus, Genetics, medicine, Humans, Genetic Predisposition to Disease, EPIC-NL, Biology, POLYMORPHISMS, Genetic association, Diabetic Endocrinology, business.industry, Cholesterol, lcsh:R, Case-control study, Human Genetics, medicine.disease, Diabetes Mellitus, Type 2, chemistry, Case-Control Studies, Hyperglycemia, Glucose Clamp Technique, lcsh:Q, business, FASTING GLUCOSE
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. © 2012 van Vliet-Ostaptchouk et al.
Published: 2012
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31. Combined genome scans for body stature in 6,602 European twins: evidence for common Caucasian loci

Author: Gonneke Willemsen, Thorkild I. A. Sørensen, Kirsten Ohm Kyvik, Leena Peltonen, Jouke-Jan Hottenga, Karri Silventoinen, Patrik K. E. Magnusson, Nancy L. Pedersen, Sampo Sammalisto, Dorret I. Boomsma, Aarno Palotie, Elisabeth Widen, Grant W. Montgomery, Beben Benyamin, Nicholas G. Martin, Markus Perola, Tim D. Spector, Jaakko Kaprio, Peter M. Visscher, Kaare Christensen, Jennifer R. Harris, Tero Hiekkalinna, and Biological Psychology
Subjects: Netherlands Twin Register (NTR), Adult, Male, Cancer Research, lcsh:QH426-470, Genetic Linkage, European Continental Ancestry Group, Genomics, Biology, Quantitative trait locus, White People, Cohort Studies, Danish, 03 medical and health sciences, Genetic linkage, Homo (Human), Twins, Dizygotic, Genetics, Humans, Human height, Molecular Biology, Genetics (clinical), Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, 0303 health sciences, Models, Statistical, Models, Genetic, Genome, Human, 030305 genetics & heredity, Linkage (Genetics), Genetics and Genomics, Heritability, Body Height, language.human_language, lcsh:Genetics, Cohort, language, Microsatellite, Female, Lod Score, Research Article, Demography
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)., Author Summary Twin cohorts provide a unique advantage for research of the role of genetics and environment behind common complex traits by reducing the variance due to environment, age, and cohort differences. The GenomEUtwin consortium consists of eight twin cohorts with the total resource of hundreds of thousands of twin pairs (http://www.genomeutwin.org). We performed quantitative family-based genetic linkage analysis for one of the most heritable human complex traits, adult stature (body height), using genome-wide scans derived from twin cohorts from Australia, Denmark, Finland, Netherlands, Sweden, and United Kingdom. Age, sex, and country were adjusted for in the data analyses. Human stature was found to be very heritable across all the cohorts and in the combined dataset. We found evidence for a shared genetic locus accounting for human stature on Chromosome 8, and suggestive evidence for loci on Chromosomes X, 7, and 20. Since twins from several countries contributed to the identified loci, an evolutionarily old genetic variant must influence stature in European-based populations. To facilitate the research in the field 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
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32. 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: Seppo Koskinen, Christian Herder, Daniel I. Chasman, Andrew R. Wood, Jonna L. Grimsby, J.F. Wilson, Day Inm., Massimo Mangino, Gonneke Willemsen, Robert W. Mahley, Cristian Pattaro, Nicole L. Glazer, T.B. Harris, Irene Pichler, M S Sandhu, D. van Heemst, Christine Proença, Martha Ganser, Robert A. Hegele, Richa Saxena, Eleftheria Zeggini, Markku Laakso, Peter Kraft, Judith B. Borja, Karen L. Mohlke, J B Richards, de Geus Ejc., Robert Sladek, Cristen J. Willer, Samy Hadjadj, S.M. Boekholdt, Gina M. Peloso, Kijoung Song, Sutapa Mukherjee, Gudmar Thorleifsson, Winston Hide, Mark I. McCarthy, Ruth E. Pakyz, Marian Beekman, Ayellet V. Segrè, Inga Prokopenko, Ping An, George Dedoussis, Danielle Posthuma, Jeanette Erdmann, Simon J. Griffin, Nilesh J. Samani, Inke R. König, Frank B. Hu, Lokki M-L., David M. Evans, Xiaohui Li, Valgerdur Steinthorsdottir, Aimo Ruokonen, A Pouta, Kerrin S. Small, Cecilia M. Lindgren, O Le Bacquer, Xijing Han, Florian Kronenberg, E Katsareli, Christian Dina, S. Gabriel, Jochen Spranger, James S. Pankow, M. Kloppenburg, Penninx Bwjh., Torben Hansen, Josh Smith, Jennie Hui, Gordon H. Williams, Mark Seielstad, Ingrid B. Borecki, Weihua Zhang, Peter P. Pramstaller, Stephen J. Sharp, Neil R. Robertson, Zee Ryl., Mike Sampson, Angela Silveira, C.M. van Duijn, Anders Hamsten, Peter Shrader, Denis Rybin, Chen Y-Di., Gunnar Sigurdsson, Michael Stumvoll, Russel Tracy, Mark O. Goodarzi, Göran Hallmans, Michael R. Erdos, Valeriya Lyssenko, Juha Saharinen, Sven Bergmann, Jeffrey R. O'Connell, Debbie A Lawlor, Thomas Meitinger, Yvonne Böttcher, Jérôme Delplanque, Sarah G. Buxbaum, Silvia Naitza, Shah Ebrahim, Graham A. Hitman, Angelo Scuteri, Aroon D. Hingorani, Heribert Schunkert, François Pattou, Claudia Lamina, A L Elliott, Sekar Kathiresan, Dawn M. Waterworth, Jennifer A. Brody, Thomas Quertermous, Leena Peltonen, Josephine M. Egan, Daniel J. Rader, J F Peden, Yarnell Jwg., Daniel S. Pearson, Pfeiffer Afh., P S Chines, N Vogelzangs, Susan Redline, Alka M. Kanaya, T B Harris, J. V. van Vliet-Ostaptchouk, Ghislain Rocheleau, Rune R. Frants, Olga D. Carlson, James G. Wilson, Melissa Garcia, Ong Rt-H., Mark J. Caulfield, Tanya M. Teslovich, Loo B-M., Beatrice Knight, Andreas Ziegler, Claudia Langenberg, Yoon Shin Cho, Paul M. Ridker, Mark J. Rieder, Praveen Sethupathy, Bert Bravenboer, J. Viikari, Matt Neville, Ioannis M. Stylianou, Andrew Walley, Jarvelin M-R., Jarred B. McAteer, Ronald M. Krauss, Augustine Kong, Oluf Pedersen, Mark J. Daly, Andrew P. Morris, Anna F. Dominiczak, Stéphane Cauchi, Michael Boehnke, Christopher J. O'Donnell, Barbara Thorand, Peter M. Nilsson, Aaron Isaacs, Deborah A. Nickerson, Roza Blagieva, Mary F. Feitosa, Nicholas J. Wareham, Robert Roberts, J S Kooner, K W van Dijk, Tiinamaija Tuomi, Paul Scheet, Lynda M. Rose, Albert V. Smith, Rafn Benediktsson, Chiara Sabatti, Candace Guiducci, Lee M. Kaplan, Aki S. Havulinna, Toby Johnson, Samuli Ripatti, Erik Ingelsson, Mario A. Morken, Carl G. P. Platou, Anke Tönjes, Qi Sun, Narisu Narisu, S J Bumpstead, Jose M. Ordovas, Alan B. Feranil, L Groop, P Chines, Sara M. Willems, Perry Jrb., Matthew A. Allison, Jan Scott, Cécile Lecoeur, Kastelein Jjp., Herman A. Taylor, Anyuan Cao, Christopher J. Groves, Lincoln D. Stein, Laura J. Scott, John Beilby, Kristin G. Ardlie, Christopher S. Franklin, Yoav Ben-Shlomo, B M Shields, N J Timpson, Marco Orrù, Amélie Bonnefond, Kiran Musunuru, Murielle Bochud, Udo Seedorf, Yongmei Liu, Guillaume Lettre, Lee J-Y., Alan R. Shuldiner, Ryan P. Welch, David J. Hunter, John Whitfield, Klaus Strassburger, Khaw K-T., Hartikainen A-L., Gunnar Sigurðsson, Lu Qi, Richard N. Bergman, G M Lathrop, Sigrid W. Fouchier, T van Herpt, David S. Siscovick, Igor Rudan, Richard M. Watanabe, Themistocles L. Assimes, Nicholas G. Martin, Ozren Polasek, Dhiraj Varma, K Kim, Oliver Hofmann, Nicholas D. Hastie, S Bumpstead, Jose C. Florez, Fernando Rivadeneira, Katharine R. Owen, Braxton D. Mitchell, Alisa K. Manning, Abbas Dehghan, Bruce Bartholow Duncan, Cisca Wijmenga, Timo T. Valle, Jaakko Kaprio, Mika Kivimäki, B Shields, Laila Simpson, Tim D. Spector, Paul W. Franks, Guangju Zhai, María Teresa Martínez-Larrad, Janssens Acjw., Kim L. Ward, Inês Barroso, Xiuqing Guo, Rosa Maria Roccasecca, Zari Dastani, Reijo Laaksonen, Wilmar Igl, Vincent Mooser, Niels Grarup, Cornelia Huth, Christian Gieger, Fabio Marroni, Jaakko Tuomilehto, Doney Asf., Andrew C. Edmondson, Christian Fuchsberger, Meena Kumari, David M. Nathan, Reedik Mägi, Solomon K. Musani, U de Faire, Knut Borch-Johnsen, Masahiro Koseki, Giuseppe Paolisso, Norman Klopp, Caroline S. Fox, Nelson B. Freimer, Mika Kähönen, Peter Henneman, Diana Zelenika, K Willems-Vandijk, Steven A. McCarroll, Paul Elliott, Wichmann H-E., J. C. Bis, Nita G. Forouhi, Antti Jula, Witteman Jcm., Fredrik Karpe, Joseph Hung, Antje Fischer-Rosinsky, Eric J. Brunner, Elena Gonzalez, Soumya Raychaudhuri, Jian'an Luan, Josée Dupuis, Joshua C. Randall, Taesung Park, Francis S. Collins, Lori L. Bonnycastle, Andrew A. Hicks, Peter Kovacs, Thomas Illig, Maja Barbalić, David Couper, Jaspal S. Kooner, Damien C. Croteau-Chonka, Gavin Lucas, P J Wagner, Young-Jin Kim, Yurii S. Aulchenko, Aurelian Bidulescu, Ingrid Meulenbelt, Pilar Galan, Iris M. Heid, Michael N. Weedon, Serena Sanna, Sarah H. Wild, Hivert M-F., Patricia B. Munroe, Johan G. Eriksson, Teresa Ferreira, Robert A. Scott, A. Sandbaek, Kenneth Rice, Veronique Vitart, Xin Yuan, Leslie A. Lange, Hilma Holm, Jorge R. Kizer, Timothy M. Frayling, Marika Kaakinen, Liu C-T., Petersen A-K., Peter Schwarz, G B Walters, Palmer Cna., Jean Tichet, Bernhard Paulweber, Ying Wu, Alyson Hall, Christopher T. Johansen, David Masson, Martin Ladouceur, Christie M. 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Wright, Karen Kapur, Xueling Sim, Philippe Froguel, K O Kyvik, T. Lauritzen, Linda S. Adair, Yavuz Ariyurek, Talin Haritunians, Toshiko Tanaka, Albert Hofman, MariaGrazia Franzosi, Nicholas L. Smith, Laura Crisponi, Andrew B. Singleton, A Uitterlinden, Bo Isomaa, Y A Kesaniemi, Anne U. Jackson, Christa Meisinger, Holly E. Syddall, Dorret I. Boomsma, Harry Campbell, Gonçalo R. Abecasis, Lyudmyla Kedenko, Christine Cavalcanti-Proença, G Crawford, Scott M. Grundy, Johnson Prv., Nuotio M-L., I Chen, J.H. Smit, Anuj Goel, M Li, David P. Strachan, Kenechi Ejebe, Beverley Balkau, Neelam Hassanali, Kristian Hveem, Pierre Meneton, R. Gwilliam, A J Swift, Caroline Hayward, J. Graessler, Carina Zabena, B. St Pourcain, Michel Marre, Margot Haun, Lyytikäinen L-P., Ben A. Oostra, Stefan Coassin, M. van Hoek, Nigel W. Rayner, John R. Thompson, Kurt Lohman, Ulla Sovio, Unnur Thorsteinsdottir, Naveed Sattar, Lyle J. Palmer, Ulf Gyllensten, A Elliott, Muredach P. 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Strachan, Dp, Reilly, Mp, Samani, Nj, Schunkert, H, Cupples, La, Ridker, Pm, Rader, Dj, Kathiresan, S., Medical Research Council (MRC), Perry, John [0000-0001-6483-3771], Wareham, Nicholas [0000-0003-1422-2993], Langenberg, Claudia [0000-0002-5017-7344], Semple, Robert [0000-0001-6539-3069], Griffin, Simon [0000-0002-2157-4797], Barroso, Ines [0000-0001-5800-4520], Soranzo, Nicole [0000-0003-1095-3852], Wheeler, Eleanor [0000-0002-8616-6444], Luan, Jian'an [0000-0003-3137-6337], Forouhi, Nita [0000-0002-5041-248X], Sharp, Stephen [0000-0003-2375-1440], Sovio, Ulla [0000-0002-0799-1105], Zhao, Jing Hua [0000-0003-4930-3582], Luben, Robert [0000-0002-5088-6343], Khaw, Kay-Tee [0000-0002-8802-2903], Sandhu, Manjinder [0000-0002-2725-142X], Apollo - University of Cambridge Repository, Biological Psychology, Functional Genomics, Neuroscience Campus Amsterdam - Attention & Cognition, EMGO+ - Lifestyle, Overweight and Diabetes, Other departments, Experimental Vascular Medicine, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Cardiology, Human genetics, Psychiatry, NCA - Attention & Cognition, EMGO - Lifestyle, overweight and diabetes, Lääketieteen yksikkö - School of Medicine, University of Tampere, Institute for Molecular Medicine Finland, Hjelt Institute (-2014), Clinicum, Department of General Practice and Primary Health Care, Department of Public Health, Haartman Institute (-2014), Transplantation Laboratory, Biostatistics Helsinki, Quantitative Genetics, Complex Disease Genetics, Genetic Epidemiology, DIAGRAM+ Consortium, MAGIC Consortium, GLGC Investigators, MuTHER Consortium, DIAGRAM Consortium, GIANT Consortium, Global B Pgen Consortium, Procardis Consortium, MAGIC investigators, GLGC Consortium, Olson, J., Kronmal, R., Robbins, J., Chaves, PH., Burke, G., Kuller, LH., Tracy, R., Gottdiener, J., Prineas, R., Becker, JT., Enright, P., Klein, R., and O'Leary, DH.
Subjects: Netherlands Twin Register (NTR), Male, Insulin Resistance/genetics, VARIANTS, 0302 clinical medicine, POPULATION, African Americans, blood/genetics, 0303 health sciences, education.field_of_study, Adiponectin/blood, Adiponectin/genetics, Asian Continental Ancestry Group, Cholesterol, HDL/genetics, Diabetes Mellitus, Type 2/genetics, European Continental Ancestry Group, Female, Gene Expression, Genetic Predisposition to Disease, Genome-Wide Association Study, Glucose Tolerance Test, Humans, Metabolic Networks and Pathways, Polymorphism, Single Nucleotide, Waist-Hip Ratio, Global B Pgen Consortium, MAGIC investigators, 3. Good health, Cholesterol, Medicine, Adiponectin, Type 2, medicine.medical_specialty, HDL, Biolääketieteet - Biomedicine, Single-nucleotide polymorphism, DIAGRAM Consortium, White People, Molecular Genetics, GLGC Consortium, 03 medical and health sciences, Asian People, SDG 3 - Good Health and Well-being, GIANT Consortium, Diabetes Mellitus, Genetics, DIAGRAM+ Consortium, GENOME-WIDE ASSOCIATION, Polymorphism, education, Biology, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 0604 Genetics, Science & Technology, GLGC Investigators, nutritional and metabolic diseases, ta3121, medicine.disease, Obesity, Black or African American, blood/genetics, African Americans, Asian Continental Ancestry Group, Cholesterol, genetics, Diabetes Mellitus, genetics, European Continental Ancestry Group, Female, Gene Expression, Genetic Predisposition to Disease, Genome-Wide Association Study, Glucose Tolerance Test, Humans, Insulin Resistance, genetics, Male, Metabolic Networks and Pathways, Polymorphism, Single Nucleotide, Waist-Hip Ratio, Endocrinology, Diabetes Mellitus, Type 2, Developmental Biology, Type 2/genetics, Cancer Research, Type 2 diabetes, QH426-470, 030204 cardiovascular system & hematology, LIPID CONCENTRATIONS, GENETICS & HEREDITY, Genetics (clinical), RISK, 2. Zero hunger, INSULIN-RESISTANCE, Glucose tolerance test, medicine.diagnostic_test, MAGIC Consortium, Single Nucleotide, ADIPOSE-TISSUE, CORONARY-ARTERY-DISEASE, Life Sciences & Biomedicine, Research Article, Clinical Research Design, GENETIC-BASIS, Population, Insulin resistance, Internal medicine, Diabetes mellitus, medicine, ddc:610, 030304 developmental biology, RECEPTOR, Cholesterol, HDL, Human Genetics, HDL/genetics, 3121 General medicine, internal medicine and other clinical medicine, MuTHER Consortium, 3111 Biomedicine, Procardis Consortium, Insulin Resistance
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, Author Summary Serum adiponectin levels are highly heritable and are inversely correlated with the risk of type 2 diabetes (T2D), coronary artery disease, stroke, and several metabolic traits. To identify common genetic variants associated with adiponectin levels and risk of T2D and metabolic traits, we conducted a meta-analysis of genome-wide association studies of 45,891 multi-ethnic individuals. In addition to confirming that variants at the ADIPOQ and CDH13 loci influence adiponectin levels, our analyses revealed that 10 new loci also affecting circulating adiponectin levels. We demonstrated that expression levels of several genes in these candidate regions are associated with serum adiponectin levels. Using a powerful novel method to assess the contribution of the identified variants with other traits using summary-level results from large-scale GWAS consortia, we provide evidence that the risk alleles for adiponectin are associated with deleterious changes in T2D risk and metabolic syndrome traits (triglycerides, HDL, post-prandial glucose, insulin, and waist-to-hip ratio), demonstrating that the identified loci, taken together, impact upon metabolic disease.
Published: 2012
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33. A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol

Author: Nancy L. Pedersen, Antti J. Kangas, James F. Wilson, Anke Toenjes, Ben A. Oostra, Janina S. Ried, Theodore Papamarkou, Angela Doering, Zoltán Kutalik, André G. Uitterlinden, Nicholas G. Martin, Antti Jula, Tõnu Esko, Bruce H. R. Wolffenbuttel, Lennart C. Karssen, Pirkka-Pekka Laurila, Åsa Johansson, Gerjan Navis, Aarno Palotie, Christian Gieger, Cisca Wijmenga, Peter P. Pramstaller, Aaron Isaacs, Inga Prokopenko, Jouke-Jan Hottenga, Massimo Mangino, Antti-Pekka Sarin, Ida Surakka, Veikko Salomaa, Taina Rantanen, Ulf Gyllensten, Nicole Soranzo, Jacqueline C.M. Witteman, Cornelia M. van Duijn, Samuli Ripatti, Albert Hofman, Nicholas W.J. Wainwright, Pasi Soininen, Leena Peltonen, Rita P. S. Middelberg, Pim van der Harst, Kirsten Ohm Kyvik, Dorret I. Boomsma, Harry Campbell, John Whitfield, Ann-Kristin Petersen, Vasiliki Lagou, Tim D. Spector, Wilmar Igl, Markus Perola, Florian Kronenberg, Maksim Struchalin, Nelson B. Freimer, Mika Kähönen, Jaakko Kaprio, Irene Mateo Leach, Fernando Rivadeneira, Mark I. McCarthy, Mika Ala-Korpela, Jorma Viikari, Andres Metspalu, Johan G. Eriksson, Eco J. C. de Geus, H.-Erich Wichmann, Grant W. Montgomery, M. S. Sandhu, Olli T. Raitakari, Michael Stumvoll, Terho Lehtimäki, Marja-Riitta Taskinen, Gonneke Willemsen, Andrew C. Heath, Igor Rudan, Yurii S. Aulchenko, Marjo-Riitta Jaervelin, Emmi Tikkanen, Claudia Lamina, Dawn M. Waterworth, Taskinen M.R., ENGAGE Consortium, Gibson, Greg, Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Cardiovascular Centre (CVC), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP), Center for Liver, Digestive and Metabolic Diseases (CLDM), Biological Psychology, EMGO+ - Mental Health, Epidemiology, Internal Medicine, Clinical Genetics, Institute for Molecular Medicine Finland, Department of Medical and Clinical Genetics, Department of Medicine, Hjelt Institute (-2014), Department of Public Health, Department of General Practice and Primary Health Care, Biostatistics Helsinki, Complex Disease Genetics, Genomics of Neurological and Neuropsychiatric Disorders, Genetic Epidemiology, and Medical Research Council (MRC)
Subjects: Netherlands Twin Register (NTR), Adipose Tissue/metabolism, Body Fat Distribution, Cadherins/genetics, Cholesterol/blood, Cholesterol/genetics, Chromosome Mapping, Chromosomes, Human, Pair 4/genetics, European Continental Ancestry Group/genetics, Genome-Wide Association Study, Genotype, Humans, Lipids/blood, Lipids/genetics, Lipoproteins/blood, Lipoproteins/genetics, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci/genetics, Risk Factors, Triglycerides/blood, Triglycerides/genetics, Waist-Hip Ratio, Genome-wide association study, 0302 clinical medicine, Genetics(clinical), Aetiology, 0303 health sciences, education.field_of_study, ta3141, ta3142, ASSOCIATION, Cadherins, Lipids, 3. Good health, Cholesterol, Adipose Tissue, DENSITY-LIPOPROTEIN CHOLESTEROL, TRIGLYCERIDE, Chromosomes, Human, Pair 4, SMOKING, Human, Lipoproteins, education, European Continental Ancestry Group, Quantitative Trait Loci, Locus (genetics), White People, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Clinical Research, Genome-Wide Association Studies, Genetics, Polymorphism, Biology, Molecular Biology, POLYMORPHISMS, Ecology, Evolution, Behavior and Systematics, 0604 Genetics, HDL CHOLESTEROL, Science & Technology, Density-lipoprotein cholesterol, HDL chloesterol, Association, Gene, Smoking, Plasma, Triglyeride, Obesity, Polymorphisms, Developmental Biology, Cancer Research, 030204 cardiovascular system & hematology, Waist–hip ratio, 2.1 Biological and endogenous factors, GENETICS & HEREDITY, Genetics (clinical), PLASMA, Single Nucleotide, ENGAGE Consortium, Pair 4/genetics, Pair 4, OBESITY, Life Sciences & Biomedicine, Research Article, LIPIDS, lcsh:QH426-470, Population, Quantitative trait locus, Chromosomes, gene, waist-to-hip ratio, cholesterol, Allele, Triglycerides, 030304 developmental biology, Whites, Human Genome, Human Genetics, Heritability, GENE, Protocadherins, lcsh:Genetics, 3111 Biomedicine
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., Author Summary Circulating serum lipids contribute greatly to the global health by affecting the risk for cardiovascular diseases. Serum lipid levels are partly inherited, and already 95 loci affecting high- and low-density lipoprotein cholesterol, total cholesterol, and triglycerides have been found. Serum lipids are also known to be affected by multiple epidemiological risk factors like body composition, lifestyle, and sex. It has been hypothesized that there are loci modifying the effects between risk factors and serum lipids, but to date only candidate gene studies for interactions have been reported. We conducted a genome-wide screen with meta-analysis approach to identify loci having interactions with epidemiological risk factors on serum lipids with over 30,000 population-based samples. When combining results from our initial datasets and 8 additional replication cohorts (maximum N = 17,102), we found a genome-wide significant locus in chromosome 4p15 with a joint P-value of 4.79×10−9 modifying the effect of waist-to-hip ratio on total cholesterol. In the area surrounding this genetic variant, there were two genes having association between the genotypes and the gene expression in adipose tissue, and we also found enrichment of association in genes belonging to lipid metabolism related functions.
Published: 2011
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34. Combined genome scans for body stature in 6602 European twins: evidence for common Caucasian loci

Author: Markus Perola, Sampo Sammalisto, Tero Hiekkalinna, Nick 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 KE Magnusson, Tim D Spector, Elisabeth Widen, Karri Silventoinen, Jaakko Kaprio, Aarno Palotie, and Leena Peltonen
Subjects: Cancer Research, Genetics, Molecular Biology, Genetics (clinical), Ecology, Evolution, Behavior and Systematics
Published: 2005
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34 results on '"Gonneke Willemsen"'

1. Integrative network analysis highlights biological processes underlying GLP-1 stimulated insulin secretion: A DIRECT study.

2. Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis.

3. Correction: Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults.

4. Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults.

5. Relative Telomere Repeat Mass in Buccal and Leukocyte-Derived DNA.

6. Correction: The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.

7. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.

8. Discovery and Fine-Mapping of Glycaemic and Obesity-Related Trait Loci Using High-Density Imputation.

9. Educational attainment influences levels of homozygosity through migration and assortative mating.

10. Effect of genome and environment on metabolic and inflammatory profiles.

11. Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers.

12. No evidence for genome-wide interactions on plasma fibrinogen by smoking, alcohol consumption and body mass index: results from meta-analyses of 80,607 subjects.

13. Identifying genetic variants for heart rate variability in the acetylcholine pathway.

14. Correction: DeepSAGE Reveals Genetic Variants Associated with Alternative Polyadenylation and Expression of Coding and Non-coding Transcripts.

15. DeepSAGE reveals genetic variants associated with alternative polyadenylation and expression of coding and non-coding transcripts.

16. The molecular genetic architecture of self-employment.

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

18. Sex differences in genetic architecture of complex phenotypes?

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

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

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

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

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

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

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

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

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

28. Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults

29. Correction: Common Variants in the Type 2 Diabetes KCNQ1 Gene Are Associated with Impairments in Insulin Secretion During Hyperglycaemic Glucose Clamp

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

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

32. Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits: A Multi-Ethnic Meta-Analysis of 45,891 Individuals

33. A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol

34. Combined genome scans for body stature in 6602 European twins: evidence for common Caucasian loci

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