학술논문
The trans-ancestral genomic architecture of glycemic traits
Document Type
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
Source
Nature Genetics. 53(6):840-860
Subject
Language
English
ISSN
1061-4036
1546-1718
1546-1718
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.