Title: The trans-ancestral genomic architecture of glycemic traits.

Authors: 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; Lifelines Cohort Study; 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, Kathry (see original citation for additional authors)

Published In Nat Genet, (2021 Jun)

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.

PubMed ID: 34059833

MeSH Terms: No MeSH terms associated with this publication