Author: "Appel, Emil V" - Searchworks@Jio Institute Digital Library Search Results

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32 results on '"Appel, Emil V"'

1. Genetic insights into resting heart rate and its role in cardiovascular disease

Author: van de Vegte, Yordi J., Eppinga, Ruben N., van der Ende, M. Yldau, Hagemeijer, Yanick P., Mahendran, Yuvaraj, Salfati, Elias, Smith, Albert V., Tan, Vanessa Y., Arking, Dan E., Ntalla, Ioanna, Appel, Emil V., Schurmann, Claudia, Brody, Jennifer A., Rueedi, Rico, Polasek, Ozren, Sveinbjornsson, Gardar, Lecoeur, Cecile, Ladenvall, Claes, Zhao, Jing Hua, Isaacs, Aaron, Wang, Lihua, Luan, Jian’an, Hwang, Shih-Jen, Mononen, Nina, Auro, Kirsi, Jackson, Anne U., Bielak, Lawrence F., Zeng, Linyao, Shah, Nabi, Nethander, Maria, Campbell, Archie, Rankinen, Tuomo, Pechlivanis, Sonali, Qi, Lu, Zhao, Wei, Rizzi, Federica, Tanaka, Toshiko, Robino, Antonietta, Cocca, Massimiliano, Lange, Leslie, Müller-Nurasyid, Martina, Roselli, Carolina, Zhang, Weihua, Kleber, Marcus E., Guo, Xiuqing, Lin, Henry J., Pavani, Francesca, Galesloot, Tessel E., Noordam, Raymond, Milaneschi, Yuri, Schraut, Katharina E., den Hoed, Marcel, Degenhardt, Frauke, Trompet, Stella, van den Berg, Marten E., Pistis, Giorgio, Tham, Yih-Chung, Weiss, Stefan, Sim, Xueling S., Li, Hengtong L., van der Most, Peter J., Nolte, Ilja M., Lyytikäinen, Leo-Pekka, Said, M. Abdullah, Witte, Daniel R., Iribarren, Carlos, Launer, Lenore, Ring, Susan M., de Vries, Paul S., Sever, Peter, Linneberg, Allan, Bottinger, Erwin P., Padmanabhan, Sandosh, Psaty, Bruce M., Sotoodehnia, Nona, Kolcic, Ivana, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Balkau, Beverley, Silva, Claudia T., Newton-Cheh, Christopher H., Nikus, Kjell, Salo, Perttu, Mohlke, Karen L., Peyser, Patricia A., Schunkert, Heribert, Lorentzon, Mattias, Lahti, Jari, Rao, Dabeeru C., Cornelis, Marilyn C., Faul, Jessica D., Smith, Jennifer A., Stolarz-Skrzypek, Katarzyna, Bandinelli, Stefania, Concas, Maria Pina, Sinagra, Gianfranco, Meitinger, Thomas, Waldenberger, Melanie, Sinner, Moritz F., Strauch, Konstantin, Delgado, Graciela E., Taylor, Kent D., Yao, Jie, Foco, Luisa, Melander, Olle, de Graaf, Jacqueline, de Mutsert, Renée, de Geus, Eco J. C., Johansson, Åsa, Joshi, Peter K., Lind, Lars, Franke, Andre, Macfarlane, Peter W., Tarasov, Kirill V., Tan, Nicholas, Felix, Stephan B., Tai, E-Shyong, Quek, Debra Q., Snieder, Harold, Ormel, Johan, Ingelsson, Martin, Lindgren, Cecilia, Morris, Andrew P., Raitakari, Olli T., Hansen, Torben, Assimes, Themistocles, Gudnason, Vilmundur, Timpson, Nicholas J., Morrison, Alanna C., Munroe, Patricia B., Strachan, David P., Grarup, Niels, Loos, Ruth J. F., Heckbert, Susan R., Vollenweider, Peter, Hayward, Caroline, Stefansson, Kari, Froguel, Philippe, Groop, Leif, Wareham, Nicholas J., van Duijn, Cornelia M., Feitosa, Mary F., O’Donnell, Christopher J., Kähönen, Mika, Perola, Markus, Boehnke, Michael, Kardia, Sharon L. R., Erdmann, Jeanette, Palmer, Colin N. A., Ohlsson, Claes, Porteous, David J., Eriksson, Johan G., Bouchard, Claude, Moebus, Susanne, Kraft, Peter, Weir, David R., Cusi, Daniele, Ferrucci, Luigi, Ulivi, Sheila, Girotto, Giorgia, Correa, Adolfo, Kääb, Stefan, Peters, Annette, Chambers, John C., Kooner, Jaspal S., März, Winfried, Rotter, Jerome I., Hicks, Andrew A., Smith, J. Gustav, Kiemeney, Lambertus A. L. M., Mook-Kanamori, Dennis O., Penninx, Brenda W. J. H., Gyllensten, Ulf, Wilson, James F., Burgess, Stephen, Sundström, Johan, Lieb, Wolfgang, Jukema, J. Wouter, Eijgelsheim, Mark, Lakatta, Edward L. M., Cheng, Ching-Yu, Dörr, Marcus, Wong, Tien-Yin, Sabanayagam, Charumathi, Oldehinkel, Albertine J., Riese, Harriette, Lehtimäki, Terho, Verweij, Niek, and van der Harst, Pim
Published: 2023
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2. Rare and low-frequency coding variants alter human adult height

Author: Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valérie, Young, Kristin L, Winkler, Thomas W, Esko, Tõnu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas GD, Ng, Maggie CY, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Banas, Bernhard, Bang, Lia E, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A, Bonnycastle, Lori L, Bork-Jensen, Jette, Bots, Michiel L, Bottinger, Erwin P, Bowden, Donald W, Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H, Broer, Linda, Burt, Amber A, Butterworth, Adam S, Carey, David J, Caulfield, Mark J, Chambers, John C, Chasman, Daniel I, Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y, Cocca, Massimiliano, Collins, Francis S, Cook, James P, Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J, Cuellar-Partida, Gabriel, Danesh, John, Davies, Gail, de Bakker, Paul IW, de Borst, Gert J, de Denus, Simon, de Groot, Mark CH, de Mutsert, Renée, Deary, Ian J, Dedoussis, George, Demerath, Ellen W, den Hollander, Anneke I, Dennis, Joe G, Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dunning, Alison M, Easton, Douglas F, Ebeling, Tapani, Edwards, Todd L, Ellinor, Patrick T, Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, and Faul, Jessica D
Subjects: Human Genome, Genetics, Aetiology, 2.1 Biological and endogenous factors, ADAMTS Proteins, Adult, Alleles, Body Height, Cell Adhesion Molecules, Female, Gene Frequency, Genetic Variation, Genome, Human, Glycoproteins, Glycosaminoglycans, Hedgehog Proteins, Humans, Intercellular Signaling Peptides and Proteins, Interferon Regulatory Factors, Interleukin-11 Receptor alpha Subunit, Male, Multifactorial Inheritance, NADPH Oxidase 4, NADPH Oxidases, Phenotype, Pregnancy-Associated Plasma Protein-A, Procollagen N-Endopeptidase, Proteoglycans, Proteolysis, Receptors, Androgen, Somatomedins, EPIC-InterAct Consortium, CHD Exome+ Consortium, ExomeBP Consortium, T2D-Genes Consortium, GoT2D Genes Consortium, Global Lipids Genetics Consortium, ReproGen Consortium, MAGIC Investigators, General Science & Technology
Abstract: Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
Published: 2017

3. Genome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci

Author: Walford, Geoffrey A, Gustafsson, Stefan, Rybin, Denis, Stančáková, Alena, Chen, Han, Liu, Ching-Ti, Hong, Jaeyoung, Jensen, Richard A, Rice, Ken, Morris, Andrew P, Mägi, Reedik, Tönjes, Anke, Prokopenko, Inga, Kleber, Marcus E, Delgado, Graciela, Silbernagel, Günther, Jackson, Anne U, Appel, Emil V, Grarup, Niels, Lewis, Joshua P, Montasser, May E, Landenvall, Claes, Staiger, Harald, Luan, Jian’an, Frayling, Timothy M, Weedon, Michael N, Xie, Weijia, Morcillo, Sonsoles, Martínez-Larrad, María Teresa, Biggs, Mary L, Chen, Yii-Der Ida, Corbaton-Anchuelo, Arturo, Færch, Kristine, Gómez-Zumaquero, Juan Miguel, Goodarzi, Mark O, Kizer, Jorge R, Koistinen, Heikki A, Leong, Aaron, Lind, Lars, Lindgren, Cecilia, Machicao, Fausto, Manning, Alisa K, Martín-Núñez, Gracia María, Rojo-Martínez, Gemma, Rotter, Jerome I, Siscovick, David S, Zmuda, Joseph M, Zhang, Zhongyang, Serrano-Rios, Manuel, Smith, Ulf, Soriguer, Federico, Hansen, Torben, Jørgensen, Torben J, Linnenberg, Allan, Pedersen, Oluf, Walker, Mark, Langenberg, Claudia, Scott, Robert A, Wareham, Nicholas J, Fritsche, Andreas, Häring, Hans-Ulrich, Stefan, Norbert, Groop, Leif, O’Connell, Jeff R, Boehnke, Michael, Bergman, Richard N, Collins, Francis S, Mohlke, Karen L, Tuomilehto, Jaakko, März, Winfried, Kovacs, Peter, Stumvoll, Michael, Psaty, Bruce M, Kuusisto, Johanna, Laakso, Markku, Meigs, James B, Dupuis, Josée, Ingelsson, Erik, and Florez, Jose C
Subjects: Biomedical and Clinical Sciences, Genetics, Prevention, Human Genome, Diabetes, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Chemokines, CC, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Insulin Receptor Substrate Proteins, Insulin Resistance, Male, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins c-bcl-2, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences
Abstract: Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI (model 3). In model 3, three variants reached genome-wide significance: rs13422522 (NYAP2; P = 8.87 × 10(-11)), rs12454712 (BCL2; P = 2.7 × 10(-8)), and rs10506418 (FAM19A2; P = 1.9 × 10(-8)). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardiometabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci.
Published: 2016

4. Estimating narrow-sense heritability using family data from admixed populations

Author: Athanasiadis, Georgios, Speed, Doug, Andersen, Mette K., Appel, Emil V. R., Grarup, Niels, Brandslund, Ivan, Jørgensen, Marit Eika, Larsen, Christina Viskum Lytken, Bjerregaard, Peter, Hansen, Torben, and Albrechtsen, Anders
Published: 2020
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5. Human pancreatic islet three-dimensional chromatin architecture provides insights into the genetics of type 2 diabetes

Author: Miguel-Escalada, Irene, Bonàs-Guarch, Silvia, Cebola, Inês, Ponsa-Cobas, Joan, Mendieta-Esteban, Julen, Atla, Goutham, Javierre, Biola M., Rolando, Delphine M. Y., Farabella, Irene, Morgan, Claire C., García-Hurtado, Javier, Beucher, Anthony, Morán, Ignasi, Pasquali, Lorenzo, Ramos-Rodríguez, Mireia, Appel, Emil V. R., Linneberg, Allan, Gjesing, Anette P., Witte, Daniel R., Pedersen, Oluf, Grarup, Niels, Ravassard, Philippe, Torrents, David, Mercader, Josep M., Piemonti, Lorenzo, Berney, Thierry, de Koning, Eelco J. P., Kerr-Conte, Julie, Pattou, François, Fedko, Iryna O., Groop, Leif, Prokopenko, Inga, Hansen, Torben, Marti-Renom, Marc A., Fraser, Peter, and Ferrer, Jorge
Published: 2019
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6. Genetic determinants of glycated hemoglobin levels in the Greenlandic Inuit population

Author: Appel, Emil V. R., Moltke, Ida, Jørgensen, Marit E., Bjerregaard, Peter, Linneberg, Allan, Pedersen, Oluf, Albrechtsen, Anders, Hansen, Torben, and Grarup, Niels
Published: 2018
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7. Author Correction: Cohort-wide deep whole genome sequencing and the allelic architecture of complex traits

Author: Gilly, Arthur, Suveges, Daniel, Kuchenbaecker, Karoline, Pollard, Martin, Southam, Lorraine, Hatzikotoulas, Konstantinos, Farmaki, Aliki-Eleni, Bjornland, Thea, Waples, Ryan, Appel, Emil V. R., Casalone, Elisabetta, Melloni, Giorgio, Kilian, Britt, Rayner, Nigel W., Ntalla, Ioanna, Kundu, Kousik, Walter, Klaudia, Danesh, John, Butterworth, Adam, Barroso, Inês, Tsafantakis, Emmanouil, Dedoussis, George, Moltke, Ida, and Zeggini, Eleftheria
Published: 2018
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8. Cohort-wide deep whole genome sequencing and the allelic architecture of complex traits

Author: Gilly, Arthur, Suveges, Daniel, Kuchenbaecker, Karoline, Pollard, Martin, Southam, Lorraine, Hatzikotoulas, Konstantinos, Farmaki, Aliki-Eleni, Bjornland, Thea, Waples, Ryan, Appel, Emil V. R., Casalone, Elisabetta, Melloni, Giorgio, Kilian, Britt, Rayner, Nigel W., Ntalla, Ioanna, Kundu, Kousik, Walter, Klaudia, Danesh, John, Butterworth, Adam, Barroso, Inês, Tsafantakis, Emmanouil, Dedoussis, George, Moltke, Ida, and Zeggini, Eleftheria
Published: 2018
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9. The trans-ancestral genomic architecture of glycemic traits

Author: Chen, Ji, Spracklen, Cassandra N., Marenne, Gaëlle, Varshney, Arushi, Corbin, Laura J., Luan, Jian'an, Willems, Sara M., Wu, Ying, Zhang, Xiaoshuai, Horikoshi, Momoko, Boutin, Thibaud S., Mägi, Reedik, Waage, Johannes, Li-Gao, Ruifang, Chan, Kei Hang Katie, Yao, Jie, Anasanti, Mila D., Chu, Audrey Y., Claringbould, Annique, Heikkinen, Jani, Hong, Jaeyoung, Hottenga, Jouke-Jan, Huo, Shaofeng, Kaakinen, Marika A., Louie, Tin, März, Winfried, Moreno-Macias, Hortensia, Ndungu, Anne, Nelson, Sarah C., Nolte, Ilja M., North, Kari E., Raulerson, Chelsea K., Ray, Debashree, Rohde, Rebecca, Rybin, Denis, Schurmann, Claudia, Sim, Xueling, Southam, Lorraine, Stewart, Isobel D., Wang, Carol A., Wang, Yujie, Wu, Peitao, Zhang, Weihua, Ahluwalia, Tarunveer S., Appel, Emil V R, Bielak, Lawrence F., Brody, Jennifer A., Burtt, Noël P, Cabrera, Claudia P., Cade, Brian E., Chai, Jin Fang, Chai, Xiaoran, Chang, Li-Ching, Chen, Chien-Hsiun, Chen, Brian H., Chitrala, Kumaraswamy Naidu, Chiu, Yen-Feng, de Haan, Hugoline G., Delgado, Graciela E., Demirkan, Ayse, Duan, Qing, Engmann, Jorgen, Fatumo, Segun A., Gayán, Javier, Giulianini, Franco, Gong, Jung Ho, Gustafsson, Stefan, Hai, Yang, Hartwig, Fernando P., He, Jing, Heianza, Yoriko, Huang, Tao, Huerta-Chagoya, Alicia, Hwang, Mi Yeong, Jensen, Richard A., Kawaguchi, Takahisa, Kentistou, Katherine A., Kim, Young Jin, Kleber, Marcus E., Kooner, Ishminder K., Lai, Shuiqing, Lange, Leslie A., Langefeld, Carl D., Lauzon, Marie, Li, Man, Ligthart, Symen, Liu, Jun, Loh, Marie, Long, Jirong, Lyssenko, Valeriya, Mangino, Massimo, Marzi, Carola, Montasser, May E., Nag, Abhishek, Nakatochi, Masahiro, Noce, Damia, Noordam, Raymond, Pistis, Giorgio, Preuss, Michael, Raffield, Laura, Rasmussen-Torvik, Laura J., Rich, Stephen S., Robertson, Neil R., Rueedi, Rico, Ryan, Kathleen, Sanna, Serena, Saxena, Richa, Schraut, Katharina E., Sennblad, Bengt, Setoh, Kazuya, Smith, Albert V., Sparsø, Thomas, Strawbridge, Rona J., Takeuchi, Fumihiko, Tan, Jingyi, Trompet, Stella, van den Akker, Erik, van der Most, Peter J., Verweij, Niek, Vogel, Mandy, Wang, Heming, Wang, Chaolong, Wang, Nan, Warren, Helen R., Wen, Wanqing, Wilsgaard, Tom, Wong, Andrew, Wood, Andrew R., Xie, Tian, Zafarmand, Mohammad Hadi, Zhao, Jing-Hua, Zhao, Wei, Amin, Najaf, Arzumanyan, Zorayr, Astrup, Arne, Bakker, Stephan J L, Baldassarre, Damiano, Beekman, Marian, Bergman, Richard N., Bertoni, Alain, Blüher, Matthias, Bonnycastle, Lori L., Bornstein, Stefan R., Bowden, Donald W., Cai, Qiuyin, Campbell, Archie, Campbell, Harry, Chang, Yi Cheng, de Geus, Eco J C, Dehghan, Abbas, Du, Shufa, Eiriksdottir, Gudny, Farmaki, Aliki Eleni, Frånberg, Mattias, Fuchsberger, Christian, Gao, Yutang, Gjesing, Anette P., Goel, Anuj, Han, Sohee, Hartman, Catharina A., Herder, Christian, Hicks, Andrew A., Hsieh, Chang-Hsun, Hsueh, Willa A., Ichihara, Sahoko, Igase, Michiya, Ikram, M Arfan, Johnson, W Craig, Jørgensen, Marit E., Joshi, Peter K., Kalyani, Rita R., Kandeel, Fouad R., Katsuya, Tomohiro, Khor, Chiea Chuen, Kiess, Wieland, Kolcic, Ivana, Kuulasmaa, Teemu, Kuusisto, Johanna, Läll, Kristi, Lam, Kelvin, Lawlor, Deborah A., Lee, Nanette R., Lemaitre, Rozenn N., Li, Honglan, Lin, Shih-Yi, Lindström, Jaana, Linneberg, Allan, Liu, Jianjun, Lorenzo, Carlos, Matsubara, Tatsuaki, Matsuda, Fumihiko, Mingrone, Geltrude, Mooijaart, Simon, Moon, Sanghoon, Nabika, Toru, Nadkarni, Girish N., Nadler, Jerry L., Nelis, Mari, Neville, Matt J., Norris, Jill M., Ohyagi, Yasumasa, Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Qi, Qibin, Raven, Dennis, Reilly, Dermot F., Reiner, Alex, Rivideneira, Fernando, Roll, Kathryn, Rudan, Igor, Sabanayagam, Charumathi, Sandow, Kevin, Sattar, Naveed, Schürmann, Annette, Shi, Jinxiu, Stringham, Heather M., Taylor, Kent D., Teslovich, Tanya M., Thuesen, Betina, Timmers, Paul R H J, Tremoli, Elena, Tsai, Michael Y., Uitterlinden, Andre, van Dam, Rob M., van Heemst, Diana, van Hylckama Vlieg, Astrid, van Vliet-Ostaptchouk, Jana V., Vangipurapu, Jagadish, Vestergaard, Henrik, Wang, Tao, Willems van Dijk, Ko, Zemunik, Tatijana, Abecasis, Gonçalo R, Adair, Linda S., Aguilar-Salinas, Carlos Alberto, Alarcón-Riquelme, Marta E., An, Ping, Aviles-Santa, Larissa, Becker, Diane M., Beilin, Lawrence J., Bergmann, Sven, Bisgaard, Hans, Black, Corri, Boehnke, Michael, Boerwinkle, Eric, Böhm, Bernhard O., Bønnelykke, Klaus, Boomsma, D.I., Bottinger, Erwin P., Buchanan, Thomas A., Canouil, Mickaël, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii-Der Ida, Cheng, Ching-Yu, Collins, Francis S., Correa, Adolfo, Cucca, Francesco, de Silva, H Janaka, Dedoussis, George, Elmståhl, Sölve, Evans, Michele K., Ferrannini, Ele, Ferrucci, Luigi, Florez, Jose C., Franks, Paul W., Frayling, Timothy M., Froguel, Philippe, Gigante, Bruna, Goodarzi, Mark O., Gordon-Larsen, Penny, Grallert, Harald, Grarup, Niels, Grimsgaard, Sameline, Groop, Leif, Gudnason, Vilmundur, Guo, Xiuqing, Hamsten, Anders, Hansen, Torben, Hayward, Caroline, Heckbert, Susan R., Horta, Bernardo L., Huang, Wei, Ingelsson, Erik, James, Pankow S., Jarvelin, Marjo-Ritta, Jonas, Jost B., Jukema, J Wouter, Kaleebu, Pontiano, Kaplan, Robert, Kardia, Sharon L R, Kato, Norihiro, Keinanen-Kiukaanniemi, Sirkka M., Kim, Bong-Jo, Kivimaki, Mika, Koistinen, Heikki A., Kooner, Jaspal S., Körner, Antje, Kovacs, Peter, Kuh, Diana, Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lakka, Timo A., Launer, Lenore J., Leander, Karin, Li, Huaixing, Lin, Xu, Lind, Lars, Lindgren, Cecilia, Liu, Simin, Loos, Ruth J F, Magnusson, Patrik K E, Mahajan, Anubha, Metspalu, Andres, Mook-Kanamori, Dennis O., Mori, Trevor A., Munroe, Patricia B., Njølstad, Inger, O'Connell, Jeffrey R., Oldehinkel, Albertine J., Ong, Ken K., Padmanabhan, Sandosh, Palmer, Colin N A, Palmer, Nicholette D., Pedersen, Oluf, Pennell, Craig E., Porteous, David J., Pramstaller, Peter P., Province, Michael A., Psaty, Bruce M., Qi, Lu, Raffel, Leslie J., Rauramaa, Rainer, Redline, Susan, Ridker, Paul M., Rosendaal, Frits R., Saaristo, Timo E., Sandhu, Manjinder, Saramies, Jouko, Schneiderman, Neil, Schwarz, Peter, Scott, Laura J., Selvin, Elizabeth, Sever, Peter, Shu, Xiao-Ou, Slagboom, P Eline, Small, Kerrin S., Smith, Blair H., Snieder, Harold, Sofer, Tamar, Sørensen, Thorkild I A, Spector, Tim D., Stanton, Alice, Steves, Claire J., Stumvoll, Michael, Sun, Liang, Tabara, Yasuharu, Tai, E Shyong, Timpson, Nicholas J., Tönjes, Anke, Tuomilehto, Jaakko, Tusie, Teresa, Uusitupa, Matti, van der Harst, Pim, van Duijn, Cornelia, Vitart, Veronique, Vollenweider, Peter, Vrijkotte, Tanja G M, Wagenknecht, Lynne E., Walker, Mark, Wang, Ya X., Wareham, Nick J., Watanabe, Richard M., Watkins, Hugh, Wei, Wen B., Wickremasinghe, Ananda R., Willemsen, Gonneke, Wilson, James F., Wong, Tien-Yin, Wu, Jer-Yuarn, Xiang, Anny H., Yanek, Lisa R., Yengo, Loïc, Yokota, Mitsuhiro, Zeggini, Eleftheria, Zheng, Wei, Zonderman, Alan B., Rotter, Jerome I., Gloyn, Anna L., McCarthy, Mark I., Dupuis, Josée, Meigs, James B., Scott, Robert A., Prokopenko, Inga, Leong, Aaron, Liu, Ching-Ti, Parker, Stephen C J, Mohlke, Karen L., Langenberg, Claudia, Wheeler, Eleanor, Morris, Andrew P., Barroso, Inês, Chen, Ji, Spracklen, Cassandra N., Marenne, Gaëlle, Varshney, Arushi, Corbin, Laura J., Luan, Jian'an, Willems, Sara M., Wu, Ying, Zhang, Xiaoshuai, Horikoshi, Momoko, Boutin, Thibaud S., Mägi, Reedik, Waage, Johannes, Li-Gao, Ruifang, Chan, Kei Hang Katie, Yao, Jie, Anasanti, Mila D., Chu, Audrey Y., Claringbould, Annique, Heikkinen, Jani, Hong, Jaeyoung, Hottenga, Jouke-Jan, Huo, Shaofeng, Kaakinen, Marika A., Louie, Tin, März, Winfried, Moreno-Macias, Hortensia, Ndungu, Anne, Nelson, Sarah C., Nolte, Ilja M., North, Kari E., Raulerson, Chelsea K., Ray, Debashree, Rohde, Rebecca, Rybin, Denis, Schurmann, Claudia, Sim, Xueling, Southam, Lorraine, Stewart, Isobel D., Wang, Carol A., Wang, Yujie, Wu, Peitao, Zhang, Weihua, Ahluwalia, Tarunveer S., Appel, Emil V R, Bielak, Lawrence F., Brody, Jennifer A., Burtt, Noël P, Cabrera, Claudia P., Cade, Brian E., Chai, Jin Fang, Chai, Xiaoran, Chang, Li-Ching, Chen, Chien-Hsiun, Chen, Brian H., Chitrala, Kumaraswamy Naidu, Chiu, Yen-Feng, de Haan, Hugoline G., Delgado, Graciela E., Demirkan, Ayse, Duan, Qing, Engmann, Jorgen, Fatumo, Segun A., Gayán, Javier, Giulianini, Franco, Gong, Jung Ho, Gustafsson, Stefan, Hai, Yang, Hartwig, Fernando P., He, Jing, Heianza, Yoriko, Huang, Tao, Huerta-Chagoya, Alicia, Hwang, Mi Yeong, Jensen, Richard A., Kawaguchi, Takahisa, Kentistou, Katherine A., Kim, Young Jin, Kleber, Marcus E., Kooner, Ishminder K., Lai, Shuiqing, Lange, Leslie A., Langefeld, Carl D., Lauzon, Marie, Li, Man, Ligthart, Symen, Liu, Jun, Loh, Marie, Long, Jirong, Lyssenko, Valeriya, Mangino, Massimo, Marzi, Carola, Montasser, May E., Nag, Abhishek, Nakatochi, Masahiro, Noce, Damia, Noordam, Raymond, Pistis, Giorgio, Preuss, Michael, Raffield, Laura, Rasmussen-Torvik, Laura J., Rich, Stephen S., Robertson, Neil R., Rueedi, Rico, Ryan, Kathleen, Sanna, Serena, Saxena, Richa, Schraut, Katharina E., Sennblad, Bengt, Setoh, Kazuya, Smith, Albert V., Sparsø, Thomas, Strawbridge, Rona J., Takeuchi, Fumihiko, Tan, Jingyi, Trompet, Stella, van den Akker, Erik, van der Most, Peter J., Verweij, Niek, Vogel, Mandy, Wang, Heming, Wang, Chaolong, Wang, Nan, Warren, Helen R., Wen, Wanqing, Wilsgaard, Tom, Wong, Andrew, Wood, Andrew R., Xie, Tian, Zafarmand, Mohammad Hadi, Zhao, Jing-Hua, Zhao, Wei, Amin, Najaf, Arzumanyan, Zorayr, Astrup, Arne, Bakker, Stephan J L, Baldassarre, Damiano, Beekman, Marian, Bergman, Richard N., Bertoni, Alain, Blüher, Matthias, Bonnycastle, Lori L., Bornstein, Stefan R., Bowden, Donald W., Cai, Qiuyin, Campbell, Archie, Campbell, Harry, Chang, Yi Cheng, de Geus, Eco J C, Dehghan, Abbas, Du, Shufa, Eiriksdottir, Gudny, Farmaki, Aliki Eleni, Frånberg, Mattias, Fuchsberger, Christian, Gao, Yutang, Gjesing, Anette P., Goel, Anuj, Han, Sohee, Hartman, Catharina A., Herder, Christian, Hicks, Andrew A., Hsieh, Chang-Hsun, Hsueh, Willa A., Ichihara, Sahoko, Igase, Michiya, Ikram, M Arfan, Johnson, W Craig, Jørgensen, Marit E., Joshi, Peter K., Kalyani, Rita R., Kandeel, Fouad R., Katsuya, Tomohiro, Khor, Chiea Chuen, Kiess, Wieland, Kolcic, Ivana, Kuulasmaa, Teemu, Kuusisto, Johanna, Läll, Kristi, Lam, Kelvin, Lawlor, Deborah A., Lee, Nanette R., Lemaitre, Rozenn N., Li, Honglan, Lin, Shih-Yi, Lindström, Jaana, Linneberg, Allan, Liu, Jianjun, Lorenzo, Carlos, Matsubara, Tatsuaki, Matsuda, Fumihiko, Mingrone, Geltrude, Mooijaart, Simon, Moon, Sanghoon, Nabika, Toru, Nadkarni, Girish N., Nadler, Jerry L., Nelis, Mari, Neville, Matt J., Norris, Jill M., Ohyagi, Yasumasa, Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Qi, Qibin, Raven, Dennis, Reilly, Dermot F., Reiner, Alex, Rivideneira, Fernando, Roll, Kathryn, Rudan, Igor, Sabanayagam, Charumathi, Sandow, Kevin, Sattar, Naveed, Schürmann, Annette, Shi, Jinxiu, Stringham, Heather M., Taylor, Kent D., Teslovich, Tanya M., Thuesen, Betina, Timmers, Paul R H J, Tremoli, Elena, Tsai, Michael Y., Uitterlinden, Andre, van Dam, Rob M., van Heemst, Diana, van Hylckama Vlieg, Astrid, van Vliet-Ostaptchouk, Jana V., Vangipurapu, Jagadish, Vestergaard, Henrik, Wang, Tao, Willems van Dijk, Ko, Zemunik, Tatijana, Abecasis, Gonçalo R, Adair, Linda S., Aguilar-Salinas, Carlos Alberto, Alarcón-Riquelme, Marta E., An, Ping, Aviles-Santa, Larissa, Becker, Diane M., Beilin, Lawrence J., Bergmann, Sven, Bisgaard, Hans, Black, Corri, Boehnke, Michael, Boerwinkle, Eric, Böhm, Bernhard O., Bønnelykke, Klaus, Boomsma, D.I., Bottinger, Erwin P., Buchanan, Thomas A., Canouil, Mickaël, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii-Der Ida, Cheng, Ching-Yu, Collins, Francis S., Correa, Adolfo, Cucca, Francesco, de Silva, H Janaka, Dedoussis, George, Elmståhl, Sölve, Evans, Michele K., Ferrannini, Ele, Ferrucci, Luigi, Florez, Jose C., Franks, Paul W., Frayling, Timothy M., Froguel, Philippe, Gigante, Bruna, Goodarzi, Mark O., Gordon-Larsen, Penny, Grallert, Harald, Grarup, Niels, Grimsgaard, Sameline, Groop, Leif, Gudnason, Vilmundur, Guo, Xiuqing, Hamsten, Anders, Hansen, Torben, Hayward, Caroline, Heckbert, Susan R., Horta, Bernardo L., Huang, Wei, Ingelsson, Erik, James, Pankow S., Jarvelin, Marjo-Ritta, Jonas, Jost B., Jukema, J Wouter, Kaleebu, Pontiano, Kaplan, Robert, Kardia, Sharon L R, Kato, Norihiro, Keinanen-Kiukaanniemi, Sirkka M., Kim, Bong-Jo, Kivimaki, Mika, Koistinen, Heikki A., Kooner, Jaspal S., Körner, Antje, Kovacs, Peter, Kuh, Diana, Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lakka, Timo A., Launer, Lenore J., Leander, Karin, Li, Huaixing, Lin, Xu, Lind, Lars, Lindgren, Cecilia, Liu, Simin, Loos, Ruth J F, Magnusson, Patrik K E, Mahajan, Anubha, Metspalu, Andres, Mook-Kanamori, Dennis O., Mori, Trevor A., Munroe, Patricia B., Njølstad, Inger, O'Connell, Jeffrey R., Oldehinkel, Albertine J., Ong, Ken K., Padmanabhan, Sandosh, Palmer, Colin N A, Palmer, Nicholette D., Pedersen, Oluf, Pennell, Craig E., Porteous, David J., Pramstaller, Peter P., Province, Michael A., Psaty, Bruce M., Qi, Lu, Raffel, Leslie J., Rauramaa, Rainer, Redline, Susan, Ridker, Paul M., Rosendaal, Frits R., Saaristo, Timo E., Sandhu, Manjinder, Saramies, Jouko, Schneiderman, Neil, Schwarz, Peter, Scott, Laura J., Selvin, Elizabeth, Sever, Peter, Shu, Xiao-Ou, Slagboom, P Eline, Small, Kerrin S., Smith, Blair H., Snieder, Harold, Sofer, Tamar, Sørensen, Thorkild I A, Spector, Tim D., Stanton, Alice, Steves, Claire J., Stumvoll, Michael, Sun, Liang, Tabara, Yasuharu, Tai, E Shyong, Timpson, Nicholas J., Tönjes, Anke, Tuomilehto, Jaakko, Tusie, Teresa, Uusitupa, Matti, van der Harst, Pim, van Duijn, Cornelia, Vitart, Veronique, Vollenweider, Peter, Vrijkotte, Tanja G M, Wagenknecht, Lynne E., Walker, Mark, Wang, Ya X., Wareham, Nick J., Watanabe, Richard M., Watkins, Hugh, Wei, Wen B., Wickremasinghe, Ananda R., Willemsen, Gonneke, Wilson, James F., Wong, Tien-Yin, Wu, Jer-Yuarn, Xiang, Anny H., Yanek, Lisa R., Yengo, Loïc, Yokota, Mitsuhiro, Zeggini, Eleftheria, Zheng, Wei, Zonderman, Alan B., Rotter, Jerome I., Gloyn, Anna L., McCarthy, Mark I., Dupuis, Josée, Meigs, James B., Scott, Robert A., Prokopenko, Inga, Leong, Aaron, Liu, Ching-Ti, Parker, Stephen C J, Mohlke, Karen L., Langenberg, Claudia, Wheeler, Eleanor, Morris, Andrew P., and Barroso, Inês
Abstract: Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
Published: 2021
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10. Genome-wide associations for birth weight and correlations with adult disease

Author: Horikoshi, Momoko, Beaumont, Robin N., Day, Felix R., Warrington, Nicole M., Kooijman, Marjolein N., Fernandez-Tajes, Juan, Feenstra, Bjarke, van Zuydam, Natalie R., Gaulton, Kyle J., Grarup, Niels, Bradfield, Jonathan P., Strachan, David P., Li-Gao, Ruifang, Ahluwalia, Tarunveer S., Kreiner, Eskil, Rueedi, Rico, Lyytikinen, Leo-Pekka, Cousminer, Diana L., Wu, Ying, Thiering, Elisabeth, Wang, Carol A., Have, Christian T., Hottenga, Jouke-Jan, Vilor-Tejedor, Natalia, Joshi, Peter K., Boh, Eileen Tai Hui, Ntalla, Ioanna, Pitknen, Niina, Mahajan, Anubha, van Leeuwen, Elisabeth M., Joro, Raimo, Lagou, Vasiliki, Nodzenski, Michael, Diver, Louise A., Zondervan, Krina T., Bustamante, Mariona, Marques-Vidal, Pedro, Mercader, Josep M., Bennett, Amanda J., Rahmioglu, Nilufer, Nyholt, Dale R., Ma, Ronald C. W., Tam, Claudia H. T., Tam, Wing Hung, Ganesh, Santhi K., van Rooij, Frank J. A., Jones, Samuel E., Loh, Po-Ru, Ruth, Katherine S., Tuke, Marcus A., Tyrrell, Jessica, Wood, Andrew R., Yaghootkar, Hanieh, Scholtens, Denise M., Paternoster, Lavinia, Prokopenko, Inga, Kovacs, Peter, Atalay, Mustafa, Willems, Sara M., Panoutsopoulou, Kalliope, Wang, Xu, Carstensen, Lisbeth, Geller, Frank, Schraut, Katharina E., Murcia, Mario, van Beijsterveldt, Catharina E. M., Willemsen, Gonneke, Appel, Emil V. R., Fonvig, Cilius E., Trier, Caecilie, Tiesler, Carla M. T., Standl, Marie, Kutalik, Zoltn, Bons-Guarch, Slvia, Hougaard, David M., Snchez, Friman, Torrents, David, Waage, Johannes, Hollegaard, Mads V., de Haan, Hugoline G., Rosendaal, Frits R., Medina-Gomez, Carolina, Ring, Susan M., Hemani, Gibran, McMahon, George, Robertson, Neil R., Groves, Christopher J., Langenberg, Claudia, Luan, Jianan, Scott, Robert A., Zhao, Jing Hua, Mentch, Frank D., MacKenzie, Scott M., Reynolds, Rebecca M., Lowe, William L., Tnjes, Anke, Stumvoll, Michael, Lindi, Virpi, Lakka, Timo A., van Duijn, Cornelia M., Kiess, Wieland, Krner, Antje, Srensen, Thorkild I. A., Niinikoski, Harri, Pahkala, Katja, Raitakari, Olli T., Zeggini, Eleftheria, Dedoussis, George V., Teo, Yik-Ying, Saw, Seang-Mei, Melbye, Mads, Campbell, Harry, Wilson, James F., Vrijheid, Martine, de Geus, Eco J. C. N., Boomsma, Dorret I., Kadarmideen, Haja N., Holm, Jens-Christian, Hansen, Torben, Sebert, Sylvain, Hattersley, Andrew T., Beilin, Lawrence J., Newnham, John P., Pennell, Craig E., Heinrich, Joachim, Adair, Linda S., Borja, Judith B., Mohlke, Karen L., Eriksson, Johan G., Widn, Elisabeth, Khnen, Mika, Viikari, Jorma S., Lehtimki, Terho, Vollenweider, Peter, Bnnelykke, Klaus, Bisgaard, Hans, Mook-Kanamori, Dennis O., Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andr G., Pisinger, Charlotta, Pedersen, Oluf, Power, Christine, Hyppnen, Elina, Wareham, Nicholas J., Hakonarson, Hakon, Davies, Eleanor, Walker, Brian R., Jaddoe, Vincent W. V., Jrvelin, Marjo-Riitta, Grant, Struan F. A., Vaag, Allan A., Lawlor, Debbie A., Frayling, Timothy M., Smith, George Davey, Morris, Andrew P., Ong, Ken K., Felix, Janine F., Timpson, Nicholas J., Perry, John R. B., Evans, David M., McCarthy, Mark I., and Freathy, Rachel M.
Subjects: Genome-wide association studies, Birth weight -- Genetic aspects -- Health aspects, Metabolic diseases -- Risk factors -- Genetic aspects, Cardiovascular diseases -- Risk factors -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract: Author(s): Momoko Horikoshi [1, 2]; Robin N. Beaumont [3]; Felix R. Day [4]; Nicole M. Warrington [5, 6]; Marjolein N. Kooijman [7, 8, 9]; Juan Fernandez-Tajes [1]; Bjarke Feenstra [10]; [...]
Published: 2016
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11. Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors

Author: Warrington, Nicole M, Beaumont, Robin N, Horikoshi, Momoko, Day, Felix R, Helgeland, Øyvind, Laurin, Charles, Bacelis, Jonas, Peng, Shouneng, Hao, Ke, Feenstra, Bjarke, Wood, Andrew R, Mahajan, Anubha, Tyrrell, Jessica, Robertson, Neil R, Rayner, N William, Qiao, Zhen, Moen, Gunn-Helen, Vaudel, Marc, Marsit, Carmen J, Chen, Jia Jue Johannes, Nodzenski, Michael, Schnurr, Theresia M, Zafarmand, Mohammad H, Bradfield, Jonathan P, Grarup, Niels, Kooijman, Marjolein N, Li-Gao, Ruifang, Geller, Frank, Ahluwalia, Tarunveer S, Paternoster, Lavinia, Rueedi, Rico, Huikari, Ville, Hottenga, Jouke-Jan, Lyytikäinen, Leo-Pekka, Cavadino, Alana, Metrustry, Sarah, Cousminer, Diana L, Wu, Ying, Thiering, Elisabeth, Wang, Carol A, Have, Christian T, Vilor-Tejedor, Natalia, Joshi, Peter K, Painter, Jodie N, Ntalla, Ioanna, Myhre, Ronny, Pitkänen, Niina, van Leeuwen, Elisabeth M, Joro, Raimo, Lagou, Vasiliki, Richmond, Rebecca C, Espinosa, Ana, Barton, Sheila J, Inskip, Hazel M, Holloway, John W, Santa-Marina, Loreto, Estivill, Xavier, Ang, Wei, Marsh, Julie A, Reichetzeder, Christoph, Marullo, Letizia, Hocher, Berthold, Lunetta, Kathryn L, Murabito, Joanne M, Relton, Caroline L, Kogevinas, Manolis, Chatzi, Leda, Allard, Catherine, Bouchard, Luigi, Hivert, Marie-France, Zhang, Ge, Muglia, Louis J, Heikkinen, Jani, Consortium, EGG, Morgen, Camilla S, van Kampen, Antoine H C, van Schaik, Barbera D C, Mentch, Frank D, Langenberg, Claudia, Luan, Jian'an, Scott, Robert A, Zhao, Jing Hua, Hemani, Gibran, Ring, Susan M, Bennett, Amanda J, Gaulton, Kyle J, Fernandez-Tajes, Juan, van Zuydam, Natalie R, Medina-Gomez, Carolina, de Haan, Hugoline G, Rosendaal, Frits R, Kutalik, Zoltán, Marques-Vidal, Pedro, Das, Shikta, Willemsen, Gonneke, Mbarek, Hamdi, Müller-Nurasyid, Martina, Standl, Marie, Appel, Emil V R, Fonvig, Cilius E, Trier, Caecilie, van Beijsterveldt, Catharina E M, Murcia, Mario, Bustamante, Mariona, Bonas-Guarch, Sílvia, Hougaard, David M, Mercader, Josep M, Linneberg, Allan, Schraut, Katharina E, Lind, Penelope A, Medland, Sarah E, Shields, Beverley M, Knight, Bridget A, Chai, Jin-Fang, Panoutsopoulou, Kalliope, Bartels, Meike, Sánchez, Friman, Stokholm, Jakob, Torrents, David, Vinding, Rebecca K, Willems, Sara M, Atalay, Mustafa, Chawes, Bo L, Kovacs, Peter, Prokopenko, Inga, Tuke, Marcus A, Yaghootkar, Hanieh, Ruth, Katherine S, Jones, Samuel E, Loh, Po-Ru, Murray, Anna, Weedon, Michael N, Tönjes, Anke, Stumvoll, Michael, Michaelsen, Kim F, Eloranta, Aino-Maija, Lakka, Timo A, van Duijn, Cornelia M, Kiess, Wieland, Körner, Antje, Niinikoski, Harri, Pahkala, Katja, Raitakari, Olli T, Jacobsson, Bo, Zeggini, Eleftheria, Dedoussis, George V, Teo, Yik-Ying, Saw, Seang-Mei, Montgomery, Grant W, Campbell, Harry, Wilson, James F, Vrijkotte, Tanja G M, Vrijheid, Martine, de Geus, Eco J C N, Hayes, M Geoffrey, Kadarmideen, Haja N, Holm, Jens-Christian, Beilin, Lawrence J, Pennell, Craig E, Heinrich, Joachim, Adair, Linda S, Borja, Judith B, Mohlke, Karen L, Eriksson, Johan G, Widén, Elisabeth E, Hattersley, Andrew T, Spector, Tim D, Kähönen, Mika, Viikari, Jorma S, Lehtimäki, Terho, Boomsma, Dorret I, Sebert, Sylvain, Vollenweider, Peter, Sørensen, Thorkild I A, Bisgaard, Hans Flinker, Bønnelykke, Klaus, Murray, Jeffrey C, Melbye, Mads, Nohr, Ellen A, Mook-Kanamori, Dennis O, Rivadeneira, Fernando, Hofman, Albert, Felix, Janine F, Jaddoe, Vincent W V, Hansen, Torben, Pisinger, Charlotta, Vaag, Allan A, Pedersen, Oluf, Uitterlinden, André G, Järvelin, Marjo-Riitta, Power, Christine, Hyppönen, Elina, Scholtens, Denise M, Lowe, William L, Davey Smith, George, Timpson, Nicholas J, Morris, Andrew P, Wareham, Nicholas J, Hakonarson, Hakon, Grant, Struan F A, Frayling, Timothy M, Lawlor, Debbie A, Njølstad, Pål R, Johansson, Stefan, Ong, Ken K, McCarthy, Mark I, Perry, John R B, Evans, David M, Freathy, Rachel M, Warrington, Nicole M, Beaumont, Robin N, Horikoshi, Momoko, Day, Felix R, Helgeland, Øyvind, Laurin, Charles, Bacelis, Jonas, Peng, Shouneng, Hao, Ke, Feenstra, Bjarke, Wood, Andrew R, Mahajan, Anubha, Tyrrell, Jessica, Robertson, Neil R, Rayner, N William, Qiao, Zhen, Moen, Gunn-Helen, Vaudel, Marc, Marsit, Carmen J, Chen, Jia Jue Johannes, Nodzenski, Michael, Schnurr, Theresia M, Zafarmand, Mohammad H, Bradfield, Jonathan P, Grarup, Niels, Kooijman, Marjolein N, Li-Gao, Ruifang, Geller, Frank, Ahluwalia, Tarunveer S, Paternoster, Lavinia, Rueedi, Rico, Huikari, Ville, Hottenga, Jouke-Jan, Lyytikäinen, Leo-Pekka, Cavadino, Alana, Metrustry, Sarah, Cousminer, Diana L, Wu, Ying, Thiering, Elisabeth, Wang, Carol A, Have, Christian T, Vilor-Tejedor, Natalia, Joshi, Peter K, Painter, Jodie N, Ntalla, Ioanna, Myhre, Ronny, Pitkänen, Niina, van Leeuwen, Elisabeth M, Joro, Raimo, Lagou, Vasiliki, Richmond, Rebecca C, Espinosa, Ana, Barton, Sheila J, Inskip, Hazel M, Holloway, John W, Santa-Marina, Loreto, Estivill, Xavier, Ang, Wei, Marsh, Julie A, Reichetzeder, Christoph, Marullo, Letizia, Hocher, Berthold, Lunetta, Kathryn L, Murabito, Joanne M, Relton, Caroline L, Kogevinas, Manolis, Chatzi, Leda, Allard, Catherine, Bouchard, Luigi, Hivert, Marie-France, Zhang, Ge, Muglia, Louis J, Heikkinen, Jani, Consortium, EGG, Morgen, Camilla S, van Kampen, Antoine H C, van Schaik, Barbera D C, Mentch, Frank D, Langenberg, Claudia, Luan, Jian'an, Scott, Robert A, Zhao, Jing Hua, Hemani, Gibran, Ring, Susan M, Bennett, Amanda J, Gaulton, Kyle J, Fernandez-Tajes, Juan, van Zuydam, Natalie R, Medina-Gomez, Carolina, de Haan, Hugoline G, Rosendaal, Frits R, Kutalik, Zoltán, Marques-Vidal, Pedro, Das, Shikta, Willemsen, Gonneke, Mbarek, Hamdi, Müller-Nurasyid, Martina, Standl, Marie, Appel, Emil V R, Fonvig, Cilius E, Trier, Caecilie, van Beijsterveldt, Catharina E M, Murcia, Mario, Bustamante, Mariona, Bonas-Guarch, Sílvia, Hougaard, David M, Mercader, Josep M, Linneberg, Allan, Schraut, Katharina E, Lind, Penelope A, Medland, Sarah E, Shields, Beverley M, Knight, Bridget A, Chai, Jin-Fang, Panoutsopoulou, Kalliope, Bartels, Meike, Sánchez, Friman, Stokholm, Jakob, Torrents, David, Vinding, Rebecca K, Willems, Sara M, Atalay, Mustafa, Chawes, Bo L, Kovacs, Peter, Prokopenko, Inga, Tuke, Marcus A, Yaghootkar, Hanieh, Ruth, Katherine S, Jones, Samuel E, Loh, Po-Ru, Murray, Anna, Weedon, Michael N, Tönjes, Anke, Stumvoll, Michael, Michaelsen, Kim F, Eloranta, Aino-Maija, Lakka, Timo A, van Duijn, Cornelia M, Kiess, Wieland, Körner, Antje, Niinikoski, Harri, Pahkala, Katja, Raitakari, Olli T, Jacobsson, Bo, Zeggini, Eleftheria, Dedoussis, George V, Teo, Yik-Ying, Saw, Seang-Mei, Montgomery, Grant W, Campbell, Harry, Wilson, James F, Vrijkotte, Tanja G M, Vrijheid, Martine, de Geus, Eco J C N, Hayes, M Geoffrey, Kadarmideen, Haja N, Holm, Jens-Christian, Beilin, Lawrence J, Pennell, Craig E, Heinrich, Joachim, Adair, Linda S, Borja, Judith B, Mohlke, Karen L, Eriksson, Johan G, Widén, Elisabeth E, Hattersley, Andrew T, Spector, Tim D, Kähönen, Mika, Viikari, Jorma S, Lehtimäki, Terho, Boomsma, Dorret I, Sebert, Sylvain, Vollenweider, Peter, Sørensen, Thorkild I A, Bisgaard, Hans Flinker, Bønnelykke, Klaus, Murray, Jeffrey C, Melbye, Mads, Nohr, Ellen A, Mook-Kanamori, Dennis O, Rivadeneira, Fernando, Hofman, Albert, Felix, Janine F, Jaddoe, Vincent W V, Hansen, Torben, Pisinger, Charlotta, Vaag, Allan A, Pedersen, Oluf, Uitterlinden, André G, Järvelin, Marjo-Riitta, Power, Christine, Hyppönen, Elina, Scholtens, Denise M, Lowe, William L, Davey Smith, George, Timpson, Nicholas J, Morris, Andrew P, Wareham, Nicholas J, Hakonarson, Hakon, Grant, Struan F A, Frayling, Timothy M, Lawlor, Debbie A, Njølstad, Pål R, Johansson, Stefan, Ong, Ken K, McCarthy, Mark I, Perry, John R B, Evans, David M, and Freathy, Rachel M
Abstract: Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.
Published: 2019

12. Estimating narrow-sense heritability from genome-wide data in admixed populations

Author: Athanasiadis, Georgios, primary, Speed, Doug, additional, Andersen, Mette K., additional, Appel, Emil V. R., additional, Grarup, Niels, additional, Brandslund, Ivan, additional, Jørgensen, Marit Eika, additional, Lytken Larsen, Christina Viskum, additional, Bjerregaard, Peter, additional, Hansen, Torben, additional, and Albrechtsen, Anders, additional
Published: 2019
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13. Tissue-Specific Alteration of Metabolic Pathways Influences Glycemic Regulation

Author: Ng, Natasha, primary, Willems, Sara M., additional, Fernandez, Juan, additional, Fine, Rebecca S., additional, Wheeler, Eleanor, additional, Wessel, Jennifer, additional, Kitajima, Hidetoshi, additional, Marenne, Gaëlle, additional, Rundle, Jana K., additional, Sim, Xueling, additional, Yeghootkar, Hanieh, additional, Beer, Nicola L., additional, Raimondo, Anne, additional, Tarasov, Andrei I., additional, Thomsen, Soren K., additional, van de Bunt, Martijn, additional, Wang, Shuai, additional, Chen, Sai, additional, Chen, Yuning, additional, Chen, Yii-Der Ida, additional, de Haan, Hugoline G., additional, Grarup, Niels, additional, Li-Gao, Ruifang, additional, Varga, Tibor V., additional, Asimit, Jennifer L, additional, Feng, Shuang, additional, Strawbridge, Rona J., additional, Kleinbrink, Erica L., additional, Ahluwalia, Tarunveer S., additional, An, Ping, additional, Appel, Emil V., additional, Arking, Dan E, additional, Auvinen, Juha, additional, Bielak, Lawrence F., additional, Bihlmeyer, Nathan A., additional, Bork-Jensen, Jette, additional, Brody, Jennifer A., additional, Campbell, Archie, additional, Chu, Audrey Y, additional, Davies, Gail, additional, Demirkan, Ayse, additional, Floyd, James S., additional, Giulianini, Franco, additional, Guo, Xiuqing, additional, Gustafsson, Stefan, additional, Hastoy, Benoit, additional, Jackson, Anne U., additional, Jakobsdottir, Johanna, additional, Järvelin, Marjo-Riitta, additional, Jensen, Richard A., additional, Kanoni, Stavroula, additional, Keinanen-Kiukaanniemi, Sirkka, additional, Li, Jin, additional, Li, Man, additional, Lohman, Kurt, additional, Lu, Yingchang, additional, Luan, Jian’an, additional, Manning, Alisa K., additional, Marten, Jonathan, additional, Marzi, Carola, additional, Meidtner, Karina, additional, Mook-Kanamori, Dennis O., additional, Muka, Taulant, additional, Pistis, Giorgio, additional, Prins, Bram, additional, Rice, Kenneth M., additional, Robertson, Neil, additional, Sanna, Serena, additional, Shi, Yuan, additional, Smith, Albert Vernon, additional, Smith, Jennifer A., additional, Southam, Lorraine, additional, Stringham, Heather M., additional, Tajuddin, Salman M., additional, Tragante, Vinicius, additional, van der Laan, Sander W., additional, Warren, Helen R., additional, Yao, Jie, additional, Yiorkas, Andrianos M., additional, Zhang, Weihua, additional, Zhao, Wei, additional, Ahlqvist, Emma, additional, Graff, Mariaelisa, additional, Highland, Heather M., additional, Justice, Anne E., additional, Lo, Ken Sin, additional, Marouli, Eirini, additional, Medina-Gomez, Carolina, additional, Afaq, Saima, additional, Alhejily, Wesam A., additional, Amin, Najaf, additional, Asselbergs, Folkert W., additional, Bonnycastle, Lori L., additional, Bots, Michiel L., additional, Brandslund, Ivan, additional, Chen, Ji, additional, Christensen, Cramer, additional, Danesh, John, additional, de Mutsert, Renée, additional, Dehghan, Abbas, additional, Ebeling, Tapani, additional, Elliott, Paul, additional, Consortium, EPIC-InterAct, additional, Farmaki, Aliki-Eleni, additional, Faul, Jessica D., additional, Franks, Paul W., additional, Franks, Steve, additional, Fritsche, Andreas, additional, Gjesing, Anette P., additional, Goodarzi, Mark O., additional, Gudnason, Vilmundur, additional, Hallmans, Göran, additional, Harris, Tamara B., additional, Herzig, Karl-Heinz, additional, Hivert, Marie-France, additional, Jansson, Jan-Håkan, additional, Jhun, Min A., additional, Beck Jørgensen, Torben, additional, Jørgensen, Marit E., additional, Jousilahti, Pekka, additional, Kajantie, Eero, additional, Karaleftheri, Maria, additional, Kardia, Sharon L.R., additional, Kinnunen, Leena, additional, Koistinena, Heikki A., additional, Komulainen, Pirjo, additional, Kovacs, Peter, additional, Kuusisto, Johanna, additional, Laakso, Markku, additional, Lange, Leslie A., additional, Launer, Lenore J., additional, Lee, Jung-Jin, additional, Leong, Aaron, additional, Lindström, Jaana, additional, Fox, Jocelyn E. Manning, additional, Männistö, Satu, additional, Maruthur, Nisa M., additional, Moilanen, Leena, additional, Mulas, Antonella, additional, Nalls, Mike A., additional, Neville, Matthew, additional, Pankow, James S., additional, Pattie, Alison, additional, Petersen, Eva R. B., additional, Puolijoki, Hannu, additional, Rasheed, Asif, additional, Redmond, Paul, additional, Renström, Frida, additional, Roden, Michael, additional, Saleheen, Danish, additional, Saltevo, Juha, additional, Savonen, Kai, additional, Sébert, Sylvain P., additional, Skaaby, Tea, additional, Small, Kerrin S., additional, Stančáková, Alena, additional, Stokholm, Jakob, additional, Strauch, Konstantin, additional, Tai, E-Shyong, additional, Taylor, Kent D., additional, Thuesen, Betina H., additional, Tönjes, Anke, additional, Tsafantakis, Emmanouil, additional, Tuomi, Tiinamaija, additional, Tuomilehto, Jaakko, additional, Group, Understanding Society Scientific, additional, Uusitupa, Matti I., additional, Vääräsmäki, Marja, additional, Vaartjes, Ilonca, additional, Zoledziewska, Magdalena, additional, Abecasis, Goncalo, additional, Balkau, Beverley, additional, Bisgaard, Hans, additional, Blakemore, Alexandra I., additional, Blüher, Matthias, additional, Boeing, Heiner, additional, Boerwinkle, Eric, additional, Bønnelykke, Klaus, additional, Bottinger, Erwin P., additional, Caulfield, Mark J., additional, Chambers, John C., additional, Chasman, Daniel I., additional, Cheng, Ching-Yu, additional, Clark, Anne, additional, Collins, Francis S., additional, Coresh, Josef, additional, Cucca, Francesco, additional, de Borst, Gert J., additional, Deary, Ian J., additional, Dedoussis, George, additional, Deloukas, Panos, additional, den Ruijter, Hester M., additional, Dupuis, Josée, additional, Evans, Michele K., additional, Ferrannini, Ele, additional, Franco, Oscar H., additional, Grallert, Harald, additional, Groop, Leif, additional, Hansen, Torben, additional, Hattersley, Andrew T., additional, Hayward, Caroline, additional, Hirschhorn, Joel N., additional, Ikram, M. Arfan, additional, Ingelsson, Erik, additional, Karpe, Fredrik, additional, Kaw, Kay-Tee, additional, Kiess, Wieland, additional, Kooner, Jaspal S., additional, Körner, Antje, additional, Lakka, Timo, additional, Langenberg, Claudia, additional, Lind, Lars, additional, Lindgren, Cecilia M., additional, Linneberg, Allan, additional, Lipovich, Leonard, additional, Liu, Ching-Ti, additional, Liu, Jun, additional, Liu, Yongmei, additional, Loos, Ruth J. F., additional, MacDonald, Patrick E., additional, Mohlke, Karen L., additional, Morris, Andrew D., additional, Munroe, Patricia B., additional, Murray, Alison, additional, Padmanabhan, Sandosh, additional, Palmer, Colin N. A., additional, Pasterkamp, Gerard, additional, Pedersen, Oluf, additional, Peyser, Patricia A., additional, Polasek, Ozren, additional, Porteous, David, additional, Province, Michael A., additional, Psaty, Bruce M., additional, Rauramaa, Rainer, additional, Ridker, Paul M., additional, Rolandsson, Olov, additional, Rorsman, Patrik, additional, Rosendaal, Frits, additional, Rudan, Igor, additional, Salomaa, Veikko, additional, Schulze, Matthias B., additional, Sladek, Robert, additional, Smith, Blair H., additional, Spector, Timothy D., additional, Starr, John M., additional, Stumvoll, Michael, additional, van Duijn, Cornelia M., additional, Walker, Mark, additional, Wareham, Nick J., additional, Weir, David R., additional, Wilson, James G., additional, Wong, Tien Yin, additional, Zeggini, Eleftheria, additional, Zonderman, Alan B., additional, Rotter, Jerome I., additional, Morris, Andrew P., additional, Boehnke, Michael, additional, Florez, Jose, additional, McCarthy, Mark I., additional, Meigs, James B., additional, Mahajan, Anubha, additional, Scott, Robert A., additional, Gloyn, Anna L., additional, and Barroso, Ines, additional
Published: 2019
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14. Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes

Author: Barcelona Supercomputing Center, Bonàs-Guarch, Sílvia, Guindo-Martínez, Marta, Miguel-Escalada, Irene, Grarup, Niels, Sebastian, David, Rodriguez-Fos, Elias, Sánchez, Friman, Planas-Fèlix, Mercè, Cortes-Sánchez, Paula, González, Santi, Timshel, Pascal, Pers, Tune H., Morgan, Claire C., Moran, Ignasi, Atla, Goutham, González, Juan R., Puiggros, Montserrat, Martí, Jonathan, Andersson, Ehm A., Díaz, Carlos, Badia Sala, Rosa Maria, Udler, Miriam, Leong, Aaron, Kaur, Varindepal, Flannick, Jason, Jorgensen, Torben, Linneberg, Allan, Jorgensen, Marit E., Witte, Daniel R., Christensen, Cramer, Brandslund, Ivan, Appel, Emil V., Scott, Robert A., Luan, Jian' an, Langenberg, Claudia, Wareham, Nicholas J., Pedersen, Oluf, Zorzano, Antonio, Florez, Jose C., Hansen, Torben, Ferrer, Jorge, Mercader, Josep M., Torrents, David, Barcelona Supercomputing Center, Bonàs-Guarch, Sílvia, Guindo-Martínez, Marta, Miguel-Escalada, Irene, Grarup, Niels, Sebastian, David, Rodriguez-Fos, Elias, Sánchez, Friman, Planas-Fèlix, Mercè, Cortes-Sánchez, Paula, González, Santi, Timshel, Pascal, Pers, Tune H., Morgan, Claire C., Moran, Ignasi, Atla, Goutham, González, Juan R., Puiggros, Montserrat, Martí, Jonathan, Andersson, Ehm A., Díaz, Carlos, Badia Sala, Rosa Maria, Udler, Miriam, Leong, Aaron, Kaur, Varindepal, Flannick, Jason, Jorgensen, Torben, Linneberg, Allan, Jorgensen, Marit E., Witte, Daniel R., Christensen, Cramer, Brandslund, Ivan, Appel, Emil V., Scott, Robert A., Luan, Jian' an, Langenberg, Claudia, Wareham, Nicholas J., Pedersen, Oluf, Zorzano, Antonio, Florez, Jose C., Hansen, Torben, Ferrer, Jorge, Mercader, Josep M., and Torrents, David
Abstract: The reanalysis of existing GWAS data represents a powerful and cost-effective opportunity to gain insights into the genetics of complex diseases. By reanalyzing publicly available type 2 diabetes (T2D) genome-wide association studies (GWAS) data for 70,127 subjects, we identify seven novel associated regions, five driven by common variants (LYPLAL1, NEUROG3, CAMKK2, ABO, and GIP genes), one by a low-frequency (EHMT2), and one driven by a rare variant in chromosome Xq23, rs146662057, associated with a twofold increased risk for T2D in males. rs146662057 is located within an active enhancer associated with the expression of Angiotensin II Receptor type 2 gene (AGTR2), a modulator of insulin sensitivity, and exhibits allelic specific activity in muscle cells. Beyond providing insights into the genetics and pathophysiology of T2D, these results also underscore the value of reanalyzing publicly available data using novel genetic resources and analytical approaches., This work has been sponsored by the grant SEV-2011-00067 of Severo Ochoa Program, awarded by the Spanish Government. This work was supported by an EFSD/Lilly research fellowship. Josep M. Mercader was supported by Sara Borrell Fellowship from the Instituto Carlos III and Beatriu de Pinós fellowship from the Agency for Management of University and Research Grants (AGAUR). Sílvia Bonàs was FI-DGR Fellowship from FI-DGR 2013 from Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR, Generalitat de Catalunya). This study makes use of data generated by the WTCCC. A full list of the investigators who contributed to the generation of the data is available from www.wtccc.org.uk. Funding for the project was provided by the Wellcome Trust under award 076113. This study also makes use of data generated by the UK10K Consortium, derived from samples from UK10K COHORT IMPUTATION (EGAS00001000713). A full list of the investigators who contributed to the generation of the data is available in www.UK10K.org. Funding for UK10K was provided by the Wellcome Trust under award WT091310. We acknowledge PRACE for awarding us to access MareNostrum supercomputer, based in Spain at Barcelona. The technical support group, particularly Pablo Ródenas and Jorge Rodríguez, from the Barcelona Supercomputing Center is gratefully acknowledged. This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 667191. Mercè Planas-Fèlix is funded by the Obra Social Fundación la Caixa fellowship under the Severo Ochoa 2013 program. Work from Irene Miguel-Escalada, Ignasi Moran, Goutham Atla, and Jorge Ferrer was supported by the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre, the Wellcome Trust (WT101033), Ministerio de Economía y Competitividad (BFU2014-54284-R) and Horizon 2020 (667191). Irene Miguel-Escalada has received funding from the European Union’s Horizon 2020 research and innovation progr, Peer Reviewed, Postprint (published version)
Published: 2018

15. Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes

Author: Bonàs-Guarch, Sílvia, Guindo-Martínez, Marta, Miguel-Escalada, Irene, Grarup, Niels, Sebastian, David, Rodriguez-Fos, Elias, Sánchez, Friman, Planas-Fèlix, Mercè, Cortes-Sánchez, Paula, González, Santi, Timshel, Pascal, Pers, Tune H, Morgan, Claire C, Moran, Ignasi, Atla, Goutham, González, Juan R, Puiggros, Montserrat, Martí, Jonathan, Andersson, Ehm A, Díaz, Carlos, Badia, Rosa M, Udler, Miriam, Leong, Aaron, Kaur, Varindepal, Flannick, Jason, Jørgensen, Torben, Linneberg, Allan, Jørgensen, Marit E, Witte, Daniel R, Christensen, Cramer, Brandslund, Ivan, Appel, Emil V, Scott, Robert A, Luan, Jian'an, Langenberg, Claudia, Wareham, Nicholas J, Pedersen, Oluf, Zorzano, Antonio, Florez, Jose C, Hansen, Torben, Ferrer, Jorge, Mercader, Josep Maria, Torrents, David, Bonàs-Guarch, Sílvia, Guindo-Martínez, Marta, Miguel-Escalada, Irene, Grarup, Niels, Sebastian, David, Rodriguez-Fos, Elias, Sánchez, Friman, Planas-Fèlix, Mercè, Cortes-Sánchez, Paula, González, Santi, Timshel, Pascal, Pers, Tune H, Morgan, Claire C, Moran, Ignasi, Atla, Goutham, González, Juan R, Puiggros, Montserrat, Martí, Jonathan, Andersson, Ehm A, Díaz, Carlos, Badia, Rosa M, Udler, Miriam, Leong, Aaron, Kaur, Varindepal, Flannick, Jason, Jørgensen, Torben, Linneberg, Allan, Jørgensen, Marit E, Witte, Daniel R, Christensen, Cramer, Brandslund, Ivan, Appel, Emil V, Scott, Robert A, Luan, Jian'an, Langenberg, Claudia, Wareham, Nicholas J, Pedersen, Oluf, Zorzano, Antonio, Florez, Jose C, Hansen, Torben, Ferrer, Jorge, Mercader, Josep Maria, and Torrents, David
Abstract: The reanalysis of existing GWAS data represents a powerful and cost-effective opportunity to gain insights into the genetics of complex diseases. By reanalyzing publicly available type 2 diabetes (T2D) genome-wide association studies (GWAS) data for 70,127 subjects, we identify seven novel associated regions, five driven by common variants (LYPLAL1, NEUROG3, CAMKK2, ABO, and GIP genes), one by a low-frequency (EHMT2), and one driven by a rare variant in chromosome Xq23, rs146662057, associated with a twofold increased risk for T2D in males. rs146662057 is located within an active enhancer associated with the expression of Angiotensin II Receptor type 2 gene (AGTR2), a modulator of insulin sensitivity, and exhibits allelic specific activity in muscle cells. Beyond providing insights into the genetics and pathophysiology of T2D, these results also underscore the value of reanalyzing publicly available data using novel genetic resources and analytical approaches.
Published: 2018

16. Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes

Author: Ministerio de Economía y Competitividad (España), European Foundation for the Study of Diabetes, Instituto de Salud Carlos III, Generalitat de Catalunya, Wellcome Trust, European Commission, Fundación la Caixa, National Institute for Health Research (UK), Novo Nordisk Foundation, Badia, Rosa M. [0000-0003-2941-5499], Bonàs-Guarch, Silvia, Guindo-Martínez, M., Miguel-Escalada, I., Niels Grarup, Sebastian, David, Rodriguez-Fos, Elias, Sánchez, Friman, Planas-Fèlix, Mercè, Cortes-Sánchez, Paula, González, Santi, Timshel, Pascal, Pers, Tune H., Morgan, Claire C., Moran, Ignasi, Atla, Goutham, González, Juan R., Puiggros, Montserrat, Martí, Jonathan, Andersson, Ehm A., Díaz, Carlos, Badia, Rosa M., Udler, Miriam, Leong, Aaron, Kaur, Varindepal, Flannick, Jason, Jørgensen, Torben, Linneberg, Allan, Jørgensen, Marit E., Witte, Daniel R., Christensen, Cramer, Brandslund, Ivan, Appel, Emil V., Scott, Robert A., Luan, Jian’an, Langenberg, Claudia, Wareham, Nicholas J., Pedersen, Oluf, Zorzano, Antonio, Florez, Jose C., Hansen, Torben, Ferrer, Jorge, Mercader, Josep Maria, Torrents, David, Ministerio de Economía y Competitividad (España), European Foundation for the Study of Diabetes, Instituto de Salud Carlos III, Generalitat de Catalunya, Wellcome Trust, European Commission, Fundación la Caixa, National Institute for Health Research (UK), Novo Nordisk Foundation, Badia, Rosa M. [0000-0003-2941-5499], Bonàs-Guarch, Silvia, Guindo-Martínez, M., Miguel-Escalada, I., Niels Grarup, Sebastian, David, Rodriguez-Fos, Elias, Sánchez, Friman, Planas-Fèlix, Mercè, Cortes-Sánchez, Paula, González, Santi, Timshel, Pascal, Pers, Tune H., Morgan, Claire C., Moran, Ignasi, Atla, Goutham, González, Juan R., Puiggros, Montserrat, Martí, Jonathan, Andersson, Ehm A., Díaz, Carlos, Badia, Rosa M., Udler, Miriam, Leong, Aaron, Kaur, Varindepal, Flannick, Jason, Jørgensen, Torben, Linneberg, Allan, Jørgensen, Marit E., Witte, Daniel R., Christensen, Cramer, Brandslund, Ivan, Appel, Emil V., Scott, Robert A., Luan, Jian’an, Langenberg, Claudia, Wareham, Nicholas J., Pedersen, Oluf, Zorzano, Antonio, Florez, Jose C., Hansen, Torben, Ferrer, Jorge, Mercader, Josep Maria, and Torrents, David
Abstract: The reanalysis of existing GWAS data represents a powerful and cost-effective opportunity to gain insights into the genetics of complex diseases. By reanalyzing publicly available type 2 diabetes (T2D) genome-wide association studies (GWAS) data for 70,127 subjects, we identify seven novel associated regions, five driven by common variants (LYPLAL1, NEUROG3, CAMKK2, ABO, and GIP genes), one by a low-frequency (EHMT2), and one driven by a rare variant in chromosome Xq23, rs146662057, associated with a twofold increased risk for T2D in males. rs146662057 is located within an active enhancer associated with the expression of Angiotensin II Receptor type 2 gene (AGTR2), a modulator of insulin sensitivity, and exhibits allelic specific activity in muscle cells. Beyond providing insights into the genetics and pathophysiology of T2D, these results also underscore the value of reanalyzing publicly available data using novel genetic resources and analytical approaches.
Published: 2018

17. Publisher Correction: Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes

Author: Bonàs-Guarch, Sílvia, primary, Guindo-Martínez, Marta, additional, Miguel-Escalada, Irene, additional, Grarup, Niels, additional, Sebastian, David, additional, Rodriguez-Fos, Elias, additional, Sánchez, Friman, additional, Planas-Fèlix, Mercè, additional, Cortes-Sánchez, Paula, additional, González, Santi, additional, Timshel, Pascal, additional, Pers, Tune H., additional, Morgan, Claire C., additional, Moran, Ignasi, additional, Atla, Goutham, additional, González, Juan R., additional, Puiggros, Montserrat, additional, Martí, Jonathan, additional, Andersson, Ehm A., additional, Díaz, Carlos, additional, Badia, Rosa M., additional, Udler, Miriam, additional, Leong, Aaron, additional, Kaur, Varindepal, additional, Flannick, Jason, additional, Jørgensen, Torben, additional, Linneberg, Allan, additional, Jørgensen, Marit E., additional, Witte, Daniel R., additional, Christensen, Cramer, additional, Brandslund, Ivan, additional, Appel, Emil V., additional, Scott, Robert A., additional, Luan, Jian’an, additional, Langenberg, Claudia, additional, Wareham, Nicholas J., additional, Pedersen, Oluf, additional, Zorzano, Antonio, additional, Florez, Jose C, additional, Hansen, Torben, additional, Ferrer, Jorge, additional, Mercader, Josep Maria, additional, and Torrents, David, additional
Published: 2018
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18. Cohort-wide deep whole genome sequencing and the allelic architecture of complex traits

Author: Gilly, Arthur, primary, Suveges, Daniel, additional, Kuchenbaecker, Karoline, additional, Pollard, Martin, additional, Southam, Lorraine, additional, Hatzikotoulas, Konstantinos, additional, Farmaki, Aliki-Eleni, additional, Bjornland, Thea, additional, Waples, Ryan, additional, Appel, Emil V. R., additional, Casalone, Elisabetta, additional, Melloni, Giorgio, additional, Kilian, Britt, additional, Rayner, Nigel W., additional, Ntalla, Ioanna, additional, Kundu, Kousik, additional, Walter, Klaudia, additional, Danesh, John, additional, Butterworth, Adam, additional, Barroso, Inês, additional, Tsafantakis, Emmanouil, additional, Dedoussis, George, additional, Moltke, Ida, additional, and Zeggini, Eleftheria, additional
Published: 2018
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19. Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes

Author: Bonàs-Guarch, Sílvia, primary, Guindo-Martínez, Marta, additional, Miguel-Escalada, Irene, additional, Grarup, Niels, additional, Sebastian, David, additional, Rodriguez-Fos, Elias, additional, Sánchez, Friman, additional, Planas-Fèlix, Mercè, additional, Cortes-Sánchez, Paula, additional, González, Santi, additional, Timshel, Pascal, additional, Pers, Tune H., additional, Morgan, Claire C., additional, Moran, Ignasi, additional, Atla, Goutham, additional, González, Juan R., additional, Puiggros, Montserrat, additional, Martí, Jonathan, additional, Andersson, Ehm A., additional, Díaz, Carlos, additional, Badia, Rosa M., additional, Udler, Miriam, additional, Leong, Aaron, additional, Kaur, Varindepal, additional, Flannick, Jason, additional, Jørgensen, Torben, additional, Linneberg, Allan, additional, Jørgensen, Marit E., additional, Witte, Daniel R., additional, Christensen, Cramer, additional, Brandslund, Ivan, additional, Appel, Emil V., additional, Scott, Robert A., additional, Luan, Jian’an, additional, Langenberg, Claudia, additional, Wareham, Nicholas J., additional, Pedersen, Oluf, additional, Zorzano, Antonio, additional, Florez, Jose C, additional, Hansen, Torben, additional, Ferrer, Jorge, additional, Mercader, Josep Maria, additional, and Torrents, David, additional
Published: 2018
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20. Rare and low-frequency coding variants alter human adult height

Author: Pharmacoepidemiology and Clinical Pharmacology, Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valérie, Young, Kristin L, Winkler, Thomas W, Esko, Tõnu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas G D, Ng, Maggie C Y, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Banas, Bernhard, Bang, Lia E, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boeing, Heiner, Boerwinkle, Eric, de Groot, Mark C H, EPIC-InterAct Consortium, Pharmacoepidemiology and Clinical Pharmacology, Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valérie, Young, Kristin L, Winkler, Thomas W, Esko, Tõnu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas G D, Ng, Maggie C Y, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Banas, Bernhard, Bang, Lia E, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boeing, Heiner, Boerwinkle, Eric, de Groot, Mark C H, and EPIC-InterAct Consortium
Published: 2017

21. Rare and low-frequency coding variants alter human adult height

Author: Circulatory Health, Team Medisch, Cardiovasculaire Epi Team 5, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, CMM Groep Kaaij, Brain, Infection & Immunity, Zorgeenheid Vaatchirurgie Medisch, CDL Upod, Other research (not in main researchprogram), Onderzoek, CDL Cluster Onderzoek en Onderwijs, Experimentele Afd. Cardiologie 1, Onderzoek Precision medicine, Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valérie, Young, Kristin L, Winkler, Thomas W, Esko, Tõnu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas G D, Ng, Maggie C Y, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Bots, Michiel L, de Bakker, Paul I W, de Borst, Gert J, de Groot, Mark C H, Kahn, René S, Ophoff, RA, Pasterkamp, Gerard, van der Laan, Sander W, van Setten, Jessica, EPIC InterAct Consortium, Circulatory Health, Team Medisch, Cardiovasculaire Epi Team 5, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, CMM Groep Kaaij, Brain, Infection & Immunity, Zorgeenheid Vaatchirurgie Medisch, CDL Upod, Other research (not in main researchprogram), Onderzoek, CDL Cluster Onderzoek en Onderwijs, Experimentele Afd. Cardiologie 1, Onderzoek Precision medicine, Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valérie, Young, Kristin L, Winkler, Thomas W, Esko, Tõnu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas G D, Ng, Maggie C Y, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Bots, Michiel L, de Bakker, Paul I W, de Borst, Gert J, de Groot, Mark C H, Kahn, René S, Ophoff, RA, Pasterkamp, Gerard, van der Laan, Sander W, van Setten, Jessica, and EPIC InterAct Consortium
Published: 2017

22. Genome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci

Author: Walford, Geoffrey A., Gustafsson, Stefan, Rybin, Denis, Stancakova, Alena, Chen, Han, Liu, Ching-Ti, Hong, Jaeyoung, Jensen, Richard A., Rice, Ken, Morris, Andrew P., Magi, Reedik, Toenjes, Anke, Prokopenko, Inga, Kleber, Marcus E., Delgado, Graciela, Silbernagel, Guenther, Jackson, Anne U., Appel, Emil V., Grarup, Niels, Lewis, Joshua P., Montasser, May E., Ladenvall, Claes, Staiger, Harald, Luan, Jian'an, Frayling, Timothy M., Weedon, Michael N., Xie, Weijia, Morcillo, Sonsoles, Teresa Martinez-Larrad, Maria, Biggs, Mary L., Chen, Yii-Der Ida, Corbaton-Anchuelo, Arturo, Faerch, Kristine, Miguel Gomez-Zumaquero, Juan, Goodarzi, Mark O., Kizer, Jorge R., Koistinen, Heikki A., Leong, Aaron, Lind, Lars, Lindgren, Cecilia, Machicao, Fausto, Manning, Alisa K., Maria Martin-Nunez, Gracia, Rojo-Martinez, Gemma, Rotter, Jerome I., Siscovick, David S., Zmuda, Joseph M., Zhang, Zhongyang, Serrano-Rios, Manuel, Smith, Ulf, Soriguer, Federico, Hansen, Torben, Jorgensen, Torben J., Linnenberg, Allan, Pedersen, Oluf, Walker, Mark, Langenberg, Claudia, Scott, Robert A., Wareham, Nicholas J., Fritsche, Andreas, Haering, Hans-Ulrich, Stefan, Norbert, Groop, Leif, O'Connell, Jeff R., Boehnke, Michael, Bergman, Richard N., Collins, Francis S., Mohlke, Karen L., Tuomilehto, Jaakko, Maerz, Winfried, Kovacs, Peter, Stumvoll, Michael, Psaty, Bruce M., Kuusisto, Johanna, Laakso, Markku, Meigs, James B., Dupuis, Josee, Ingelsson, Erik, Florez, Jose C., Walford, Geoffrey A., Gustafsson, Stefan, Rybin, Denis, Stancakova, Alena, Chen, Han, Liu, Ching-Ti, Hong, Jaeyoung, Jensen, Richard A., Rice, Ken, Morris, Andrew P., Magi, Reedik, Toenjes, Anke, Prokopenko, Inga, Kleber, Marcus E., Delgado, Graciela, Silbernagel, Guenther, Jackson, Anne U., Appel, Emil V., Grarup, Niels, Lewis, Joshua P., Montasser, May E., Ladenvall, Claes, Staiger, Harald, Luan, Jian'an, Frayling, Timothy M., Weedon, Michael N., Xie, Weijia, Morcillo, Sonsoles, Teresa Martinez-Larrad, Maria, Biggs, Mary L., Chen, Yii-Der Ida, Corbaton-Anchuelo, Arturo, Faerch, Kristine, Miguel Gomez-Zumaquero, Juan, Goodarzi, Mark O., Kizer, Jorge R., Koistinen, Heikki A., Leong, Aaron, Lind, Lars, Lindgren, Cecilia, Machicao, Fausto, Manning, Alisa K., Maria Martin-Nunez, Gracia, Rojo-Martinez, Gemma, Rotter, Jerome I., Siscovick, David S., Zmuda, Joseph M., Zhang, Zhongyang, Serrano-Rios, Manuel, Smith, Ulf, Soriguer, Federico, Hansen, Torben, Jorgensen, Torben J., Linnenberg, Allan, Pedersen, Oluf, Walker, Mark, Langenberg, Claudia, Scott, Robert A., Wareham, Nicholas J., Fritsche, Andreas, Haering, Hans-Ulrich, Stefan, Norbert, Groop, Leif, O'Connell, Jeff R., Boehnke, Michael, Bergman, Richard N., Collins, Francis S., Mohlke, Karen L., Tuomilehto, Jaakko, Maerz, Winfried, Kovacs, Peter, Stumvoll, Michael, Psaty, Bruce M., Kuusisto, Johanna, Laakso, Markku, Meigs, James B., Dupuis, Josee, Ingelsson, Erik, and Florez, Jose C.
Abstract: Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI (model 3). In model 3, three variants reached genome-wide significance: rs13422522 (NYAP2; P = 8.87 x 10(-11)), rs12454712 (BCL2; P = 2.7 x 10(-8)), and rs10506418 (FAM19A2; P = 1.9 x 10(-8)). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardiometabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci., Funding:This work was supported by National Institutes of Health grant DK099249 (to G.A.W.). Grant support was provided to cohorts. For METSIM, the study was funded by the Academy of Finland (grants 77299 and 124243). For Sorbs, the work was supported by grants from the German Research Council (DFG-SFB 1052, "Obesity mechanisms," A01, C01, B03, and SPP 1629 TO 718/2-1), the German Diabetes Association, and the Diabetes Hilfs-und Forschungsfonds Deutschland (DHFD). This work was further supported by the Federal Ministry of Education and Research (BMBF), Germany, FKZ (01EO1501, AD2-060E to P.K.), and by the Boehringer Ingelheim Foundation. For FHS, the study was supported by the National Heart, Lung, and Blood Institute (contract nos. N02-HL-6-4278 [supporting its contract with Affymetrix, Inc., for genotyping services], N01-HC-25195, HL084756, and HHSN268201500001I) and the National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK078616 to J.D., U01-DK085526 to H.C. and J.D., 2R01 DK078616 and K24 DK080140 to J.M.). A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. A.K.M. was supported by American Diabetes Association Research Foundation (grant 7-12-MN-02). For CHS, research was supported by National Heart, Lung, and Blood Institute contract nos. HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and grant nos. U01HL080295, HL105756, and HL120393, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided by R01AG023629 from the National Institute on Aging (NIA). For ULSAM, the project was supported by the Knut and Alice Wallenberg Foundation (Wallenberg Academy Fellow), the European Research Council (ERC Starting Grant), the Swe
Published: 2016
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23. Prospective Studies Exploring the Possible Impact of an ID3 Polymorphism on Changes in Obesity Measures.

Author: Svendstrup, Mathilde, Appel, Emil V. R., Sandholt, Camilla H., Ahluwalia, Tarunveer S., Ängquist, Lars H., Thuesen, Betina H., Jørgensen, Marit E., Pedersen, Oluf, Grarup, Niels, Hansen, Torben, Sørensen, Thorkild I. A., and Vestergaard, Henrik
Subjects: GENETIC polymorphisms, OBESITY, BODY weight, METABOLIC disorders, BODY mass index, PROTEIN metabolism, ANIMAL experimentation, COMPARATIVE studies, LONGITUDINAL method, RESEARCH methodology, MEDICAL cooperation, PROTEINS, RESEARCH, EVALUATION research, CASE-control method, GENOTYPES
Abstract: Objective: Changes in fat mass depend on adipogenesis and angiogenesis, mechanisms regulated by the inhibitor of differentiation-3 (ID3). Id3 knockout mice showed attenuated increases in BMI and visceral fat mass. We hypothesized that the ID3 missense variant (rs11574-A) would lead to an attenuated increase over time in fat mass, BMI, waist circumference (WC), and waist-hip ratio (WHR) in humans.Methods: The genotyped study populations included the Obesity Research Group - Genetics (ORGGEN) cohort, a cohort of men with obesity (N = 716) and of randomly selected men (N = 826) from the Danish draft register who were examined at mean ages of 20 and 46 years, and the Inter99 (N = 6,116) and Health2006 (N = 2,761) cohorts, two population-based samples of middle-aged people, followed up after 5 years.Results: In meta-analyses of all data, no association was found between rs11574-A and changes in BMI, WC, WHR, or fat mass. We found an association between rs11574-A and cross-sectional BMI (N = 10,359, β: -0.16 kg/m2 per allele, 95% CI: -0.30 to -0.01, P = 0.033) and fat mass (N = 4,188, β: -0.52 kg/m2 per allele, 95% CI: -1.03 to -0.01, P = 0.046).Conclusions: No consistent impact of the genetic variant on changes in fat mass, BMI, or fat distribution was found in three Danish cohorts. [ABSTRACT FROM AUTHOR]
Published: 2018
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24. Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors

Author: Warrington, Nicole M., Beaumont, Robin N., Horikoshi, Momoko, Day, Felix R., Helgeland, Øyvind, Laurin, Charles, Bacelis, Jonas, Peng, Shouneng, Hao, Ke, Feenstra, Bjarke, Wood, Andrew R., Mahajan, Anubha, Tyrrell, Jessica, Robertson, Neil R., Rayner, N. William, Qiao, Zhen, Moen, Gunn-Helen, Vaudel, Marc, Marsit, Carmen J., Chen, Jia, Nodzenski, Michael, Schnurr, Theresia M., Zafarmand, Mohammad H., Bradfield, Jonathan P., Grarup, Niels, Kooijman, Marjolein N., Li-Gao, Ruifang, Geller, Frank, Ahluwalia, Tarunveer S., Paternoster, Lavinia, Rueedi, Rico, Huikari, Ville, Hottenga, Jouke-Jan, Lyytikäinen, Leo-Pekka, Cavadino, Alana, Metrustry, Sarah, Cousminer, Diana L., Wu, Ying, Thiering, Elisabeth, Wang, Carol A., Have, Christian T., Vilor-Tejedor, Natalia, Joshi, Peter K., Painter, Jodie N., Ntalla, Ioanna, Myhre, Ronny, Pitkänen, Niina, van Leeuwen, Elisabeth M., Joro, Raimo, Lagou, Vasiliki, Richmond, Rebecca C., Espinosa, Ana, Barton, Sheila J., Inskip, Hazel M., Holloway, John W., Santa-Marina, Loreto, Estivill, Xavier, Ang, Wei, Marsh, Julie A., Reichetzeder, Christoph, Marullo, Letizia, Hocher, Berthold, Lunetta, Kathryn L., Murabito, Joanne M., Relton, Caroline L., Kogevinas, Manolis, Chatzi, Leda, Allard, Catherine, Bouchard, Luigi, Hivert, Marie-France, Zhang, Ge, Muglia, Louis J., Heikkinen, Jani, Morgen, Camilla S., van Kampen, Antoine H. C., van Schaik, Barbera D. C., Mentch, Frank D., Langenberg, Claudia, Luan, Jian’an, Scott, Robert A., Zhao, Jing Hua, Hemani, Gibran, Ring, Susan M., Bennett, Amanda J., Gaulton, Kyle J., Fernandez-Tajes, Juan, van Zuydam, Natalie R., Medina-Gomez, Carolina, de Haan, Hugoline G., Rosendaal, Frits R., Kutalik, Zoltán, Marques-Vidal, Pedro, Das, Shikta, Willemsen, Gonneke, Mbarek, Hamdi, Müller-Nurasyid, Martina, Standl, Marie, Appel, Emil V. R., Fonvig, Cilius E., Trier, Caecilie, van Beijsterveldt, Catharina E. M., Murcia, Mario, Bustamante, Mariona, Bonas-Guarch, Sílvia, Hougaard, David M., Mercader, Josep M., Linneberg, Allan, Schraut, Katharina E., Lind, Penelope A., Medland, Sarah E., Shields, Beverley M., Knight, Bridget A., Chai, Jin-Fang, Panoutsopoulou, Kalliope, Bartels, Meike, Sánchez, Friman, Stokholm, Jakob, Torrents, David, Vinding, Rebecca K., Willems, Sara M., Atalay, Mustafa, Chawes, Bo L., Kovacs, Peter, Prokopenko, Inga, Tuke, Marcus A., Yaghootkar, Hanieh, Ruth, Katherine S., Jones, Samuel E., Loh, Po-Ru, Murray, Anna, Weedon, Michael N., Tönjes, Anke, Stumvoll, Michael, Michaelsen, Kim F., Eloranta, Aino-Maija, Lakka, Timo A., van Duijn, Cornelia M., Kiess, Wieland, Körner, Antje, Niinikoski, Harri, Pahkala, Katja, Raitakari, Olli T., Jacobsson, Bo, Zeggini, Eleftheria, Dedoussis, George V., Teo, Yik-Ying, Saw, Seang-Mei, Montgomery, Grant W., Campbell, Harry, Wilson, James F., Vrijkotte, Tanja G. M., Vrijheid, Martine, de Geus, Eco J. C. N., Hayes, M. Geoffrey, Kadarmideen, Haja N., Holm, Jens-Christian, Beilin, Lawrence J., Pennell, Craig E., Heinrich, Joachim, Adair, Linda S., Borja, Judith B., Mohlke, Karen L., Eriksson, Johan G., Widén, Elisabeth E., Hattersley, Andrew T., Spector, Tim D., Kähönen, Mika, Viikari, Jorma S., Lehtimäki, Terho, Boomsma, Dorret I., Sebert, Sylvain, Vollenweider, Peter, Sørensen, Thorkild I. A., Bisgaard, Hans, Bønnelykke, Klaus, Murray, Jeffrey C., Melbye, Mads, Nohr, Ellen A., Mook-Kanamori, Dennis O., Rivadeneira, Fernando, Hofman, Albert, Felix, Janine F., Jaddoe, Vincent W. V., Hansen, Torben, Pisinger, Charlotta, Vaag, Allan A., Pedersen, Oluf, Uitterlinden, André G., Järvelin, Marjo-Riitta, Power, Christine, Hyppönen, Elina, Scholtens, Denise M., Lowe, William L., Davey Smith, George, Timpson, Nicholas J., Morris, Andrew P., Wareham, Nicholas J., Hakonarson, Hakon, Grant, Struan F. A., Frayling, Timothy M., Lawlor, Debbie A., Njølstad, Pål R., Johansson, Stefan, Ong, Ken K., McCarthy, Mark I., Perry, John R. B., Evans, David M., and Freathy, Rachel M.
Abstract: Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n= 321,223) and offspring birth weight (n= 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight–blood pressure association is attributable to genetic effects, and not to intrauterine programming.
Published: 2019
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25. Comparative Analyses of QTLs Influencing Obesity and Metabolic Phenotypes in Pigs and Humans

Author: Pant, Sameer D., primary, Karlskov-Mortensen, Peter, additional, Jacobsen, Mette J., additional, Cirera, Susanna, additional, Kogelman, Lisette J. A., additional, Bruun, Camilla S., additional, Mark, Thomas, additional, Jørgensen, Claus B., additional, Grarup, Niels, additional, Appel, Emil V. R., additional, Galjatovic, Ehm A. A., additional, Hansen, Torben, additional, Pedersen, Oluf, additional, Guerin, Maryse, additional, Huby, Thierry, additional, Lesnik, Philipppe, additional, Meuwissen, Theo H. E., additional, Kadarmideen, Haja N., additional, and Fredholm, Merete, additional
Published: 2015
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26. Publisher Correction: Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes

Author: Bonàs-Guarch, Sílvia, Guindo-Martínez, Marta, Miguel-Escalada, Irene, Grarup, Niels, Sebastian, David, Rodriguez-Fos, Elias, Sánchez, Friman, Planas-Fèlix, Mercè, Cortes-Sánchez, Paula, González, Santi, Timshel, Pascal, Pers, Tune H., Morgan, Claire C., Moran, Ignasi, Atla, Goutham, González, Juan R., Puiggros, Montserrat, Martí, Jonathan, Andersson, Ehm A., Díaz, Carlos, Badia, Rosa M., Udler, Miriam, Leong, Aaron, Kaur, Varindepal, Flannick, Jason, Jørgensen, Torben, Linneberg, Allan, Jørgensen, Marit E., Witte, Daniel R., Christensen, Cramer, Brandslund, Ivan, Appel, Emil V., Scott, Robert A., Luan, Jian’an, Langenberg, Claudia, Wareham, Nicholas J., Pedersen, Oluf, Zorzano, Antonio, Florez, Jose C, Hansen, Torben, Ferrer, Jorge, Mercader, Josep Maria, and Torrents, David
Published: 2018
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27. Rare and low-frequency coding variants alter human adult height

Author: Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valérie, Young, Kristin L, Winkler, Thomas W, Esko, Tõnu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas GD, Ng, Maggie CY, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Banas, Bernhard, Bang, Lia E, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A, Bonnycastle, Lori L, Bork-Jensen, Jette, Bots, Michiel L, Bottinger, Erwin P, Bowden, Donald W, Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H, Broer, Linda, Burt, Amber A, Butterworth, Adam S, Carey, David J, Caulfield, Mark J, Chambers, John C, Chasman, Daniel I, Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y, Cocca, Massimiliano, Collins, Francis S, Cook, James P, Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J, Cuellar-Partida, Gabriel, Danesh, John, Davies, Gail, de Bakker, Paul IW, de Borst, Gert J., de Denus, Simon, de Groot, Mark CH, de Mutsert, Renée, Deary, Ian J, Dedoussis, George, Demerath, Ellen W, den Hollander, Anneke I, Dennis, Joe G, Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dunning, Alison M, Easton, Douglas F, Ebeling, Tapani, Edwards, Todd L, Ellinor, Patrick T, Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Faul, Jessica D, Feitosa, Mary F, Feng, Shuang, Ferrannini, Ele, Ferrario, Marco M, Ferrieres, Jean, Florez, Jose C, Ford, Ian, Fornage, Myriam, Franks, Paul W, Frikke-Schmidt, Ruth, Galesloot, Tessel E, Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Giri, Ayush, Girotto, Giorgia, Gordon, Scott D, Gordon-Larsen, Penny, Gorski, Mathias, Grarup, Niels, Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B, Hattersley, Andrew T, Hayward, Caroline, He, Liang, Heid, Iris M, Heikkilä, Kauko, Helgeland, Øyvind, Hernesniemi, Jussi, Hewitt, Alex W, Hocking, Lynne J, Hollensted, Mette, Holmen, Oddgeir L, Hovingh, G. Kees, Howson, Joanna MM, Hoyng, Carel B, Huang, Paul L, Hveem, Kristian, Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U, Jansson, Jan-Håkan, Jarvik, Gail P, Jensen, Gorm B, Jhun, Min A, Jia, Yucheng, Jiang, Xuejuan, Johansson, Stefan, Jørgensen, Marit E, Jørgensen, Torben, Jousilahti, Pekka, Jukema, J Wouter, Kahali, Bratati, Kahn, René S, Kähönen, Mika, Kamstrup, Pia R, Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon LR, Karpe, Fredrik, Kee, Frank, Keeman, Renske, Kiemeney, Lambertus A, Kitajima, Hidetoshi, Kluivers, Kirsten B, Kocher, Thomas, Komulainen, Pirjo, Kontto, Jukka, Kooner, Jaspal S, Kooperberg, Charles, Kovacs, Peter, Kriebel, Jennifer, Kuivaniemi, Helena, Küry, Sébastien, Kuusisto, Johanna, La Bianca, Martina, Laakso, Markku, Lakka, Timo A, Lange, Ethan M, Lange, Leslie A, Langefeld, Carl D, Langenberg, Claudia, Larson, Eric B, Lee, I-Te, Lehtimäki, Terho, Lewis, Cora E, Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Li-An, Lin, Xu, Lind, Lars, Lindström, Jaana, Linneberg, Allan, Liu, Yeheng, Liu, Yongmei, Lophatananon, Artitaya, Luan, Jian'an, Lubitz, Steven A, Lyytikäinen, Leo-Pekka, Mackey, David A, Madden, Pamela AF, Manning, Alisa K, Männistö, Satu, Marenne, Gaëlle, Marten, Jonathan, Martin, Nicholas G, Mazul, Angela L, Meidtner, Karina, Metspalu, Andres, Mitchell, Paul, Mohlke, Karen L, Mook-Kanamori, Dennis O, Morgan, Anna, Morris, Andrew D, Morris, Andrew P, Müller-Nurasyid, Martina, Munroe, Patricia B, Nalls, Mike A, Nauck, Matthias, Nelson, Christopher P, Neville, Matt, Nielsen, Sune F, Nikus, Kjell, Njølstad, Pål R, Nordestgaard, Børge G, Ntalla, Ioanna, O'Connel, Jeffrey R, Oksa, Heikki, Loohuis, Loes M Olde, Ophoff, Roel A, Owen, Katharine R, Packard, Chris J, Padmanabhan, Sandosh, Palmer, Colin NA, Pasterkamp, Gerard, Patel, Aniruddh P, Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L, Peloso, Gina M, Pennell, Craig E, Perola, Markus, Perry, James A, Perry, John R.B., Person, Thomas N, Pirie, Ailith, Polasek, Ozren, Posthuma, Danielle, Raitakari, Olli T, Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F, Reiner, Alex P, Renström, Frida, Ridker, Paul M, Rioux, John D, Robertson, Neil, Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J, Sandow, Kevin, Sapkota, Yadav, Sattar, Naveed, Schmidt, Marjanka K, Schreiner, Pamela J, Schulze, Matthias B, Scott, Robert A, Segura-Lepe, Marcelo P, Shah, Svati, Sim, Xueling, Sivapalaratnam, Suthesh, Small, Kerrin S, Smith, Albert Vernon, Smith, Jennifer A, Southam, Lorraine, Spector, Timothy D, Speliotes, Elizabeth K, Starr, John M, Steinthorsdottir, Valgerdur, Stringham, Heather M, Stumvoll, Michael, Surendran, Praveen, Hart, Leen M ‘t, Tansey, Katherine E, Tardif, Jean-Claude, Taylor, Kent D, Teumer, Alexander, Thompson, Deborah J, Thorsteinsdottir, Unnur, Thuesen, Betina H, Tönjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P, Uher, Rudolf, Uitterlinden, André G, Ulivi, Sheila, van der Laan, Sander W, Van Der Leij, Andries R, van Duijn, Cornelia M, van Schoor, Natasja M, van Setten, Jessica, Varbo, Anette, Varga, Tibor V, Varma, Rohit, Edwards, Digna R Velez, Vermeulen, Sita H, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F, Vozzi, Diego, Walker, Mark, Wang, Feijie, Wang, Carol A, Wang, Shuai, Wang, Yiqin, Wareham, Nicholas J, Warren, Helen R, Wessel, Jennifer, Willems, Sara M, Wilson, James G, Witte, Daniel R, Woods, Michael O, Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M, Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zheng, He, Zhou, Wei, Rotter, Jerome I, Boehnke, Michael, Kathiresan, Sekar, McCarthy, Mark I, Willer, Cristen J, Stefansson, Kari, Borecki, Ingrid B, Liu, Dajiang J, North, Kari E, Heard-Costa, Nancy L, Pers, Tune H, Lindgren, Cecilia M, Oxvig, Claus, Kutalik, Zoltán, Rivadeneira, Fernando, Loos, Ruth JF, Frayling, Timothy M, Hirschhorn, Joel N, Deloukas, Panos, and Lettre, Guillaume
Abstract: Summary Height is a highly heritable, classic polygenic trait with ∼700 common associated variants identified so far through genome-wide association studies. Here, we report 83 height-associated coding variants with lower minor allele frequencies (range of 0.1-4.8%) and effects of up to 2 cm/allele (e.g. in IHH, STC2, AR and CRISPLD2), >10 times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (+1-2 cm/allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates (e.g. ADAMTS3, IL11RA, NOX4) and pathways (e.g. proteoglycan/glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate to large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
Published: 2016
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28. Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes

Author: Bonàs-Guarch, Sílvia, Guindo-Martínez, Marta, Miguel-Escalada, Irene, Grarup, Niels, Sebastian, David, Rodriguez-Fos, Elias, Sánchez, Friman, Planas-Fèlix, Mercè, Cortes-Sánchez, Paula, González, Santi, Timshel, Pascal, Pers, Tune H, Morgan, Claire C, Moran, Ignasi, Atla, Goutham, González, Juan R, Puiggros, Montserrat, Martí, Jonathan, Andersson, Ehm A, Díaz, Carlos, Badia, Rosa M, Udler, Miriam, Leong, Aaron, Kaur, Varindepal, Flannick, Jason, Jørgensen, Torben, Linneberg, Allan, Jørgensen, Marit E, Witte, Daniel R, Christensen, Cramer, Brandslund, Ivan, Appel, Emil V, Scott, Robert A, Luan, Jian'an, Langenberg, Claudia, Wareham, Nicholas J, Pedersen, Oluf, Zorzano, Antonio, Florez, Jose C, Hansen, Torben, Ferrer, Jorge, Mercader, Josep Maria, and Torrents, David
Subjects: Male, Chromosomes, Human, X, Genotype, Models, Genetic, Risk Factors, Humans, Gene Regulatory Networks, Genetic Predisposition to Disease, Insulin Resistance, Polymorphism, Single Nucleotide, Alleles, 3. Good health, Genome-Wide Association Study
Abstract: The reanalysis of existing GWAS data represents a powerful and cost-effective opportunity to gain insights into the genetics of complex diseases. By reanalyzing publicly available type 2 diabetes (T2D) genome-wide association studies (GWAS) data for 70,127 subjects, we identify seven novel associated regions, five driven by common variants (LYPLAL1, NEUROG3, CAMKK2, ABO, and GIP genes), one by a low-frequency (EHMT2), and one driven by a rare variant in chromosome Xq23, rs146662057, associated with a twofold increased risk for T2D in males. rs146662057 is located within an active enhancer associated with the expression of Angiotensin II Receptor type 2 gene (AGTR2), a modulator of insulin sensitivity, and exhibits allelic specific activity in muscle cells. Beyond providing insights into the genetics and pathophysiology of T2D, these results also underscore the value of reanalyzing publicly available data using novel genetic resources and analytical approaches.

29. Genome-wide associations for birth weight and correlations with adult disease

Author: Standl, Marie, Grarup, Niels, Mercader, Josep M., Nodzenski, Michael, Warrington, Nicole M., Felix, Janine F., Tuke, Marcus A., Hofman, Albert, Mohlke, Karen L., Strachan, David P., Kadarmideen, Haja N., Bonàs-Guarch, Sílvia, Scholtens, Denise M., Panoutsopoulou, Kalliope, Kovacs, Peter, Li-Gao, Ruifang, Langenberg, Claudia, Bønnelykke, Klaus, Morris, Andrew P., Reynolds, Rebecca M., Sørensen, Thorkild I. A., Day, Felix R., Freathy, Rachel M., Schraut, Katharina E., Feenstra, Bjarke, Bisgaard, Hans, Torrents, David, Carstensen, Lisbeth, De Haan, Hugoline G., Newnham, John P., Ruth, Katherine S., Ring, Susan M., Sánchez, Friman, Pisinger, Charlotta, Bustamante, Mariona, Robertson, Neil R., Rahmioglu, Nilufer, Kutalik, Zoltán, Rueedi, Rico, Boomsma, Dorret I., Horikoshi, Momoko, Rosendaal, Frits R., Van Beijsterveldt, Catharina E. M., Campbell, Harry, Mentch, Frank D., Kreiner, Eskil, Stumvoll, Michael, Fonvig, Cilius E., Willems, Sara M., Willemsen, Gonneke, Prokopenko, Inga, Beaumont, Robin N., Wu, Ying, Geller, Frank, Smith, George Davey, Bennett, Amanda J., Pitkänen, Niina, Dedoussis, George V., Vilor-Tejedor, Natalia, Lindi, Virpi, Jones, Samuel E., Trier, Caecilie, Tam, Claudia H. T., Vrijheid, Martine, Pedersen, Oluf, Tyrrell, Jessica, Widén, Elisabeth, Wareham, Nicholas J., Boh, Eileen Tai Hui, Uitterlinden, André G., De Geus, Eco J. C. N., Mahajan, Anubha, Kiess, Wieland, Vaag, Allan A., Wang, Carol A., Ganesh, Santhi K., Eriksson, Johan G., Van Leeuwen, Elisabeth M., Ong, Ken K., Timpson, Nicholas J., Luan, Jian'An, Murcia, Mario, Hottenga, Jouke-Jan, Van Rooij, Frank J. A., Thiering, Elisabeth, Mook-Kanamori, Dennis O., Davies, Eleanor, Van Zuydam, Natalie R., Ntalla, Ioanna, Vollenweider, Peter, Zhao, Jing Hua, Sebert, Sylvain, Hakonarson, Hakon, Walker, Brian R., Appel, Emil V. R., Joshi, Peter K., Tönjes, Anke, Adair, Linda S., Lakka, Timo A., Have, Christian T., Körner, Antje, Nyholt, Dale R., McMahon, George, Jaddoe, Vincent W. V., Tam, Wing Hung, Tiesler, Carla M. T., Teo, Yik-Ying, Atalay, Mustafa, Raitakari, Olli T., Niinikoski, Harri, Paternoster, Lavinia, Melbye, Mads, Rivadeneira, Fernando, Kähönen, Mika, Bradfield, Jonathan P., Beilin, Lawrence J., Hyppönen, Elina, Loh, Po-Ru, Wood, Andrew R., Ma, Ronald C. W., Scott, Robert A., Viikari, Jorma S., Medina-Gomez, Carolina, Pahkala, Katja, Hansen, Torben, Wilson, James F., Zeggini, Eleftheria, Kooijman, Marjolein N., Joro, Raimo, Cousminer, Diana L., Borja, Judith B., Frayling, Timothy M., Järvelin, Marjo-Riitta, Perry, John R. B., Holm, Jens-Christian, Lagou, Vasiliki, MacKenzie, Scott M., Fernandez-Tajes, Juan, Evans, David M., Pennell, Craig E., McCarthy, Mark I., Waage, Johannes, Heinrich, Joachim, Ahluwalia, Tarunveer S., Grant, Struan F. A., Hemani, Gibran, Lawlor, Debbie A., Lehtimäki, Terho, Van Duijn, Cornelia M., Gaulton, Kyle J., Zondervan, Krina T., Lyytikaïnen, Leo-Pekka, Hollegaard, Mads V., Wang, Xu, Lowe, William L., Yaghootkar, Hanieh, Diver, Louise A., Hattersley, Andrew T., Groves, Christopher J., Hougaard, David M., Power, Christine, Marques-Vidal, Pedro, and Saw, Seang-Mei
Subjects: 3. Good health
Abstract: Birth weight (BW) is influenced by both foetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease1. These lifecourse associations have often been attributed to the impact of an adverse early life environment. We performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where foetal genotype was associated with BW (P

30. Human pancreatic islet three-dimensional chromatin architecture provides insights into the genetics of type 2 diabetes

Author: Lorenzo Piemonti, Goutham Atla, Torben Hansen, Claire Morgan, Inês Cebola, Jorge Ferrer, Inga Prokopenko, Irene Farabella, Irene Miguel-Escalada, Marc A. Marti-Renom, Lorenzo Pasquali, Emil V. R. Appel, Niels Grarup, Javier García-Hurtado, Leif Groop, Josep M. Mercader, Eelco J.P. de Koning, Mireia Ramos-Rodríguez, Anette P. Gjesing, Delphine M.Y. Rolando, Allan Linneberg, Sílvia Bonàs-Guarch, François Pattou, Philippe Ravassard, Daniel R. Witte, Biola M. Javierre, Julie Kerr-Conte, Joan Ponsa-Cobas, David Torrents, Anthony Beucher, Peter Fraser, Thierry Berney, Iryna O. Fedko, Ole Birger Pedersen, Julen Mendieta-Esteban, Ignasi Moran, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Research Centre For Prevention and Health, Department 84/85, Copenhagen University Hospital Glostrup, Steno Diabetes Center, University of Copenhagen = Københavns Universitet (KU), Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Steno Diabetes Center and Hagedorn Research Institute, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Barcelona Supercomputing Center - Centro Nacional de Supercomputacion (BSC - CNS), IRCCS Ospedale San Raffaele [Milan, Italy], Centre médical universitaire de Genève (CMU), Therapie Cellulaire du Diabete, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Department of Clinical Sciences, Diabetes and Endocrinology Unit, Lund University [Lund], Gene Regulation, Stem Cells and Cancer Program, CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain, The Babraham Institute, The Babraham Institute, Cambridge, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Biological Psychology, Wellcome Trust, Imperial College Healthcare NHS Trust- BRC Funding, Medical Research Council (MRC), Miguel-Escalada, Irene, Bonàs-Guarch, Silvia, Cebola, Inê, Ponsa-Cobas, Joan, Mendieta-Esteban, Julen, Atla, Goutham, Javierre, Biola M, Rolando, Delphine M Y, Farabella, Irene, Morgan, Claire C, García-Hurtado, Javier, Beucher, Anthony, Morán, Ignasi, Pasquali, Lorenzo, Ramos-Rodríguez, Mireia, Appel, Emil V R, Linneberg, Allan, Gjesing, Anette P, Witte, Daniel R, Pedersen, Oluf, Grarup, Niel, Ravassard, Philippe, Torrents, David, Mercader, Josep M, Piemonti, Lorenzo, Berney, Thierry, de Koning, Eelco J P, Kerr-Conte, Julie, Pattou, Françoi, Fedko, Iryna O, Groop, Leif, Prokopenko, Inga, Hansen, Torben, Marti-Renom, Marc A, Fraser, Peter, Ferrer, Jorge, and Hubrecht Institute for Developmental Biology and Stem Cell Research
Subjects: Epigenomics, endocrine system diseases, Metabolic disorders, Gene regulatory network, Molecular Conformation, Genome-wide association study, VARIANTS, Genome-wide association studies, Genome, Cohort Studies, 0302 clinical medicine, Genetics research, Insulin Secretion, Gene Regulatory Networks, TRANSCRIPTION, Promoter Regions, Genetic, 11 Medical and Health Sciences, ComputingMilieux_MISCELLANEOUS, Genetics, Genetics & Heredity, RISK, 0303 health sciences, geography.geographical_feature_category, ddc:617, CELL IDENTITY, Islet, Chromatin, READ ALIGNMENT, medicine.anatomical_structure, Enhancer Elements, Genetic, Life Sciences & Biomedicine, EXPRESSION, endocrine system, Biology, MECHANISMS, 03 medical and health sciences, Islets of Langerhans, SDG 3 - Good Health and Well-being, medicine, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Enhancer, Gene, 030304 developmental biology, geography, Science & Technology, Pancreatic islets, 06 Biological Sciences, SUPER-ENHANCERS, TCF7L2, Diabetes Mellitus, Type 2, Gene Expression Regulation, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, 030217 neurology & neurosurgery, Genome-Wide Association Study, Developmental Biology
Abstract: Genetic studies promise to provide insight into the molecular mechanisms underlying type 2 diabetes (T2D). Variants associated with T2D are often located in tissue-specific enhancer clusters or super-enhancers. So far, such domains have been defined through clustering of enhancers in linear genome maps rather than in three-dimensional (3D) space. Furthermore, their target genes are often unknown. We have created promoter capture Hi-C maps in human pancreatic islets. This linked diabetes-associated enhancers to their target genes, often located hundreds of kilobases away. It also revealed >1,300 groups of islet enhancers, super-enhancers and active promoters that form 3D hubs, some of which show coordinated glucose-dependent activity. We demonstrate that genetic variation in hubs impacts insulin secretion heritability, and show that hub annotations can be used for polygenic scores that predict T2D risk driven by islet regulatory variants. Human islet 3D chromatin architecture, therefore, provides a framework for interpretation of T2D genome-wide association study (GWAS) signals. This research was supported by the National Institute for Health Research Imperial Biomedical Research Centre. Work was funded by grants from the Wellcome Trust (nos. WT101033 to J.F. and WT205915 to I.P.), Horizon 2020 (Research and Innovation Programme nos. 667191, to J.F., 633595, to I.P., and 676556, to M.A.M.-R.; Marie Sklodowska-Curie 658145, to I.M.-E., and 43062 ZENCODE, to G.A.), European Research Council (nos. 789055, to J.F., and 609989, to M.A.M.-R.). Marató TV3 (no. 201611, to J.F. and M.A.M.-R.), Ministerio de Ciencia Innovación y Universidades (nos. BFU2014-54284-R, RTI2018-095666, to J.F., BFU2017-85926-P, to M.A.M.-R., IJCI-2015-23352, to I.F.), AGAUR (to M.A.M.-R.). UK Medical Research Council (no. MR/L007150/1, to P.F., MR/L02036X/1 to J.F.), World Cancer Research Fund (WCRF UK, to I.P.) and World Cancer Research Fund International (no. 2017/1641 to I.P.), Biobanking and Biomolecular Resources Research Infrastructure (nos. BBMRI-NL, NWO 184.021.007, to I.O.F.). Work in IDIBAPS, CRG and CNAG was supported by the CERCA Programme, Generalitat de Catalunya and Centros de Excelencia Severo Ochoa (no. SEV-2012-0208). Human islets were provided through the European islet distribution program for basic research supported by JDRF (no. 3-RSC-2016-160-I-X). We thank N. Ruiz-Gomez for technical assistance; R. L. Fernandes, T. Thorne (University of Reading) and A. Perdones-Montero (Imperial College London) for helpful discussions regarding Machine Learning approaches; B. Lenhard and M. Merkenschlager (London Institute of Medical Sciences, Imperial College London), F. Müller (University of Birmingham) and J. L. Gómez-Skarmeta (Centro Andaluz de Biología del Desarrollo) for critical comments on the draft; the CRG Genomics Unit; and the Imperial College High Performance Computing Service.
Published: 2019
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31. Large-scale exome array summary statistics resources for glycemic traits to aid effector gene prioritization.

Author: Willems SM, Ng NHJ, Fernandez J, Fine RS, Wheeler E, Wessel J, Kitajima H, Marenne G, Sim X, Yaghootkar H, Wang S, Chen S, Chen Y, Chen YI, Grarup N, Li-Gao R, Varga TV, Asimit JL, Feng S, Strawbridge RJ, Kleinbrink EL, Ahluwalia TS, An P, Appel EV, Arking DE, Auvinen J, Bielak LF, Bihlmeyer NA, Bork-Jensen J, Brody JA, Campbell A, Chu AY, Davies G, Demirkan A, Floyd JS, Giulianini F, Guo X, Gustafsson S, Jackson AU, Jakobsdottir J, Järvelin MR, Jensen RA, Kanoni S, Keinanen-Kiukaanniemi S, Li M, Lu Y, Luan J, Manning AK, Marten J, Meidtner K, Mook-Kanamori DO, Muka T, Pistis G, Prins B, Rice KM, Sanna S, Smith AV, Smith JA, Southam L, Stringham HM, Tragante V, van der Laan SW, Warren HR, Yao J, Yiorkas AM, Zhang W, Zhao W, Graff M, Highland HM, Justice AE, Marouli E, Medina-Gomez C, Afaq S, Alhejily WA, Amin N, Asselbergs FW, Bonnycastle LL, Bots ML, Brandslund I, Chen J, Danesh J, de Mutsert R, Dehghan A, Ebeling T, Elliott P, Farmaki AE, Faul JD, Franks PW, Franks S, Fritsche A, Gjesing AP, Goodarzi MO, Gudnason V, Hallmans G, Harris TB, Herzig KH, Hivert MF, Jørgensen T, Jørgensen ME, Jousilahti P, Kajantie E, Karaleftheri M, Kardia SLR, Kinnunen L, Koistinen HA, Komulainen P, Kovacs P, Kuusisto J, Laakso M, Lange LA, Launer LJ, Leong A, Lindström J, Manning Fox JE, Männistö S, Maruthur NM, Moilanen L, Mulas A, Nalls MA, Neville M, Pankow JS, Pattie A, Petersen ERB, Puolijoki H, Rasheed A, Redmond P, Renström F, Roden M, Saleheen D, Saltevo J, Savonen K, Sebert S, Skaaby T, Small KS, Stančáková A, Stokholm J, Strauch K, Tai ES, Taylor KD, Thuesen BH, Tönjes A, Tsafantakis E, Tuomi T, Tuomilehto J, Uusitupa M, Vääräsmäki M, Vaartjes I, Zoledziewska M, Abecasis G, Balkau B, Bisgaard H, Blakemore AI, Blüher M, Boeing H, Boerwinkle E, Bønnelykke K, Bottinger EP, Caulfield MJ, Chambers JC, Chasman DI, Cheng CY, Collins FS, Coresh J, Cucca F, de Borst GJ, Deary IJ, Dedoussis G, Deloukas P, den Ruijter HM, Dupuis J, Evans MK, Ferrannini E, Franco OH, Grallert H, Hansen T, Hattersley AT, Hayward C, Hirschhorn JN, Ikram A, Ingelsson E, Karpe F, Kaw KT, Kiess W, Kooner JS, Körner A, Lakka T, Langenberg C, Lind L, Lindgren CM, Linneberg A, Lipovich L, Liu CT, Liu J, Liu Y, Loos RJF, MacDonald PE, Mohlke KL, Morris AD, Munroe PB, Murray A, Padmanabhan S, Palmer CNA, Pasterkamp G, Pedersen O, Peyser PA, Polasek O, Porteous D, Province MA, Psaty BM, Rauramaa R, Ridker PM, Rolandsson O, Rorsman P, Rosendaal FR, Rudan I, Salomaa V, Schulze MB, Sladek R, Smith BH, Spector TD, Starr JM, Stumvoll M, van Duijn CM, Walker M, Wareham NJ, Weir DR, Wilson JG, Wong TY, Zeggini E, Zonderman AB, Rotter JI, Morris AP, Boehnke M, Florez JC, McCarthy MI, Meigs JB, Mahajan A, Scott RA, Gloyn AL, and Barroso I
Abstract: Background: Genome-wide association studies for glycemic traits have identified hundreds of loci associated with these biomarkers of glucose homeostasis. Despite this success, the challenge remains to link variant associations to genes, and underlying biological pathways., Methods: To identify coding variant associations which may pinpoint effector genes at both novel and previously established genome-wide association loci, we performed meta-analyses of exome-array studies for four glycemic traits: glycated hemoglobin (HbA1c, up to 144,060 participants), fasting glucose (FG, up to 129,665 participants), fasting insulin (FI, up to 104,140) and 2hr glucose post-oral glucose challenge (2hGlu, up to 57,878). In addition, we performed network and pathway analyses., Results: Single-variant and gene-based association analyses identified coding variant associations at more than 60 genes, which when combined with other datasets may be useful to nominate effector genes. Network and pathway analyses identified pathways related to insulin secretion, zinc transport and fatty acid metabolism. HbA1c associations were strongly enriched in pathways related to blood cell biology., Conclusions: Our results provided novel glycemic trait associations and highlighted pathways implicated in glycemic regulation. Exome-array summary statistic results are being made available to the scientific community to enable further discoveries., Competing Interests: Competing interests: Rebecca S. Fine: Rebecca S. Fine is currently employed by Vertex Pharmaceuticals Incorporated. Audrey Y Chu: Currently employed by GlaxoSmithkline. Dennis O. Mook-Kanamori: Dennis Mook-Kanamori is working as a part-time clinical research consultant for Metabolon, Inc. Paul W. Franks: PWF has been a paid consultant for Eli Lilly and Sanofi Aventis and has received research support from several pharmaceutical companies as part of a European Union Innovative Medicines Initiative (IMI) project. Mike A. Nalls: Dr. Mike A. Nalls is supported by a consulting contract between Data Tecnica International LLC and the National Institute on Aging (NIA), National Institutes of Health (NIH), Bethesda, MD, USA. Dr. Nalls also consults for Illumina Inc., the Michael J. Fox Foundation, and the University of California Healthcare. Mark J. Caulfield: MJC is Chief Scientist for Genomics England, a UK government company. Joel N. Hirschhorn: JHN is on the scientific advisory board of Camp4 Therapeutics. Erik Ingelsson: Erik Ingelsson is now an employee of GlaxoSmithKline. Anubha Mahajan: Anubha Mahajan is an employee of Genentech since January 2020, and a holder of Roche stock. Mark I McCarthy: The views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. MMcC has served on advisory panels for Pfizer, NovoNordisk and Zoe Global, has received honoraria from Merck, Pfizer, Novo Nordisk and Eli Lilly, and research funding from Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Roche, Sanofi Aventis, Servier, and Takeda. As of June 2019, MMcC is an employee of Genentech, and a holder of Roche stock. Inês Barroso: IB and spouse declare stock ownership in GlaxoSmithkline and Incyte Ltd. James B. Meigs: JBM serves as an Academic Associate for Quest Diagnostics R&D Bruce M Psaty serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Dr. Sander W. van der Laan has received Roche funding for unrelated work. Matthias Blüher received honoraria as a consultant and speaker from Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Lilly, Novo Nordisk, Novartis, Pfizer and Sanofi. Vinicius Tragante: VT became an employee of deCODE genetics/Amgen Inc. after the conclusion of this work Dr Franco is employed by ErasmusAGE, a center for aging research across the life course funded by Nestlé Nutrition (Nestec Ltd.) and Metagenics., (Copyright: © 2023 Willems SM et al.)
Published: 2023
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32. The trans-ancestral genomic architecture of glycemic traits.

Author: Chen J, Spracklen CN, Marenne G, Varshney A, Corbin LJ, Luan J, Willems SM, Wu Y, Zhang X, Horikoshi M, Boutin TS, Mägi R, Waage J, Li-Gao R, Chan KHK, Yao J, Anasanti MD, Chu AY, Claringbould A, Heikkinen J, Hong J, Hottenga JJ, Huo S, Kaakinen MA, Louie T, März W, Moreno-Macias H, Ndungu A, Nelson SC, Nolte IM, North KE, Raulerson CK, Ray D, Rohde R, Rybin D, Schurmann C, Sim X, Southam L, Stewart ID, Wang CA, Wang Y, Wu P, Zhang W, Ahluwalia TS, Appel EVR, Bielak LF, Brody JA, Burtt NP, Cabrera CP, Cade BE, Chai JF, Chai X, Chang LC, Chen CH, Chen BH, Chitrala KN, Chiu YF, de Haan HG, Delgado GE, Demirkan A, Duan Q, Engmann J, Fatumo SA, Gayán J, Giulianini F, Gong JH, Gustafsson S, Hai Y, Hartwig FP, He J, Heianza Y, Huang T, Huerta-Chagoya A, Hwang MY, Jensen RA, Kawaguchi T, Kentistou KA, Kim YJ, Kleber ME, Kooner IK, Lai S, Lange LA, Langefeld CD, Lauzon M, Li M, Ligthart S, Liu J, Loh M, Long J, Lyssenko V, Mangino M, Marzi C, Montasser ME, Nag A, Nakatochi M, Noce D, Noordam R, Pistis G, Preuss M, Raffield L, Rasmussen-Torvik LJ, Rich SS, Robertson NR, Rueedi R, Ryan K, Sanna S, Saxena R, Schraut KE, Sennblad B, Setoh K, Smith AV, Sparsø T, Strawbridge RJ, Takeuchi F, Tan J, Trompet S, van den Akker E, van der Most PJ, Verweij N, Vogel M, Wang H, Wang C, Wang N, Warren HR, Wen W, Wilsgaard T, Wong A, Wood AR, Xie T, Zafarmand MH, Zhao JH, Zhao W, Amin N, Arzumanyan Z, Astrup A, Bakker SJL, Baldassarre D, Beekman M, Bergman RN, Bertoni A, Blüher M, Bonnycastle LL, Bornstein SR, Bowden DW, Cai Q, Campbell A, Campbell H, Chang YC, de Geus EJC, Dehghan A, Du S, Eiriksdottir G, Farmaki AE, Frånberg M, Fuchsberger C, Gao Y, Gjesing AP, Goel A, Han S, Hartman CA, Herder C, Hicks AA, Hsieh CH, Hsueh WA, Ichihara S, Igase M, Ikram MA, Johnson WC, Jørgensen ME, Joshi PK, Kalyani RR, Kandeel FR, Katsuya T, Khor CC, Kiess W, Kolcic I, Kuulasmaa T, Kuusisto J, Läll K, Lam K, Lawlor DA, Lee NR, Lemaitre RN, Li H, Lin SY, Lindström J, Linneberg A, Liu J, Lorenzo C, Matsubara T, Matsuda F, Mingrone G, Mooijaart S, Moon S, Nabika T, Nadkarni GN, Nadler JL, Nelis M, Neville MJ, Norris JM, Ohyagi Y, Peters A, Peyser PA, Polasek O, Qi Q, Raven D, Reilly DF, Reiner A, Rivideneira F, Roll K, Rudan I, Sabanayagam C, Sandow K, Sattar N, Schürmann A, Shi J, Stringham HM, Taylor KD, Teslovich TM, Thuesen B, Timmers PRHJ, Tremoli E, Tsai MY, Uitterlinden A, van Dam RM, van Heemst D, van Hylckama Vlieg A, van Vliet-Ostaptchouk JV, Vangipurapu J, Vestergaard H, Wang T, Willems van Dijk K, Zemunik T, Abecasis GR, Adair LS, Aguilar-Salinas CA, Alarcón-Riquelme ME, An P, Aviles-Santa L, Becker DM, Beilin LJ, Bergmann S, Bisgaard H, Black C, Boehnke M, Boerwinkle E, Böhm BO, Bønnelykke K, Boomsma DI, Bottinger EP, Buchanan TA, Canouil M, Caulfield MJ, Chambers JC, Chasman DI, Chen YI, Cheng CY, Collins FS, Correa A, Cucca F, de Silva HJ, Dedoussis G, Elmståhl S, Evans MK, Ferrannini E, Ferrucci L, Florez JC, Franks PW, Frayling TM, Froguel P, Gigante B, Goodarzi MO, Gordon-Larsen P, Grallert H, Grarup N, Grimsgaard S, Groop L, Gudnason V, Guo X, Hamsten A, Hansen T, Hayward C, Heckbert SR, Horta BL, Huang W, Ingelsson E, James PS, Jarvelin MR, Jonas JB, Jukema JW, Kaleebu P, Kaplan R, Kardia SLR, Kato N, Keinanen-Kiukaanniemi SM, Kim BJ, Kivimaki M, Koistinen HA, Kooner JS, Körner A, Kovacs P, Kuh D, Kumari M, Kutalik Z, Laakso M, Lakka TA, Launer LJ, Leander K, Li H, Lin X, Lind L, Lindgren C, Liu S, Loos RJF, Magnusson PKE, Mahajan A, Metspalu A, Mook-Kanamori DO, Mori TA, Munroe PB, Njølstad I, O'Connell JR, Oldehinkel AJ, Ong KK, Padmanabhan S, Palmer CNA, Palmer ND, Pedersen O, Pennell CE, Porteous DJ, Pramstaller PP, Province MA, Psaty BM, Qi L, Raffel LJ, Rauramaa R, Redline S, Ridker PM, Rosendaal FR, Saaristo TE, Sandhu M, Saramies J, Schneiderman N, Schwarz P, Scott LJ, Selvin E, Sever P, Shu XO, Slagboom PE, Small KS, Smith BH, Snieder H, Sofer T, Sørensen TIA, Spector TD, Stanton A, Steves CJ, Stumvoll M, Sun L, Tabara Y, Tai ES, Timpson NJ, Tönjes A, Tuomilehto J, Tusie T, Uusitupa M, van der Harst P, van Duijn C, Vitart V, Vollenweider P, Vrijkotte TGM, Wagenknecht LE, Walker M, Wang YX, Wareham NJ, Watanabe RM, Watkins H, Wei WB, Wickremasinghe AR, Willemsen G, Wilson JF, Wong TY, Wu JY, Xiang AH, Yanek LR, Yengo L, Yokota M, Zeggini E, Zheng W, Zonderman AB, Rotter JI, Gloyn AL, McCarthy MI, Dupuis J, Meigs JB, Scott RA, Prokopenko I, Leong A, Liu CT, Parker SCJ, Mohlke KL, Langenberg C, Wheeler E, Morris AP, and Barroso I
Subjects: Alleles, Epigenesis, Genetic, Gene Expression Profiling, Genome, Human, Genome-Wide Association Study, Glycated Hemoglobin metabolism, Humans, Multifactorial Inheritance genetics, Physical Chromosome Mapping, Quantitative Trait Loci genetics, Blood Glucose genetics, Quantitative Trait, Heritable, White People genetics
Abstract: Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10 -8 ), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
Published: 2021
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32 results on '"Appel, Emil V"'

1. Genetic insights into resting heart rate and its role in cardiovascular disease

2. Rare and low-frequency coding variants alter human adult height

3. Genome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci

4. Estimating narrow-sense heritability using family data from admixed populations

5. Human pancreatic islet three-dimensional chromatin architecture provides insights into the genetics of type 2 diabetes

6. Genetic determinants of glycated hemoglobin levels in the Greenlandic Inuit population

7. Author Correction: Cohort-wide deep whole genome sequencing and the allelic architecture of complex traits

8. Cohort-wide deep whole genome sequencing and the allelic architecture of complex traits

9. The trans-ancestral genomic architecture of glycemic traits

10. Genome-wide associations for birth weight and correlations with adult disease

11. Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors

12. Estimating narrow-sense heritability from genome-wide data in admixed populations

13. Tissue-Specific Alteration of Metabolic Pathways Influences Glycemic Regulation

14. Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes

15. Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes

16. Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes

17. Publisher Correction: Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes

18. Cohort-wide deep whole genome sequencing and the allelic architecture of complex traits

19. Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes

20. Rare and low-frequency coding variants alter human adult height

21. Rare and low-frequency coding variants alter human adult height

22. Genome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci

23. Prospective Studies Exploring the Possible Impact of an ID3 Polymorphism on Changes in Obesity Measures.

24. Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors

25. Comparative Analyses of QTLs Influencing Obesity and Metabolic Phenotypes in Pigs and Humans

26. Publisher Correction: Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes

27. Rare and low-frequency coding variants alter human adult height

28. Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes

29. Genome-wide associations for birth weight and correlations with adult disease

30. Human pancreatic islet three-dimensional chromatin architecture provides insights into the genetics of type 2 diabetes

31. Large-scale exome array summary statistics resources for glycemic traits to aid effector gene prioritization.

32. The trans-ancestral genomic architecture of glycemic traits.

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32 results on '"Appel, Emil V"'

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