The trans-ancestral genomic architecture of glycemic traits
Chen, Ji; Spracklen, Cassandra N.; Marenne, Gaelle; Varshney, Arushi; Corbin, Laura J.; Luan, Jian'an; Willems, Sara M.; Wu, Ying; Zhang, Xiaoshuai; Horikoshi, Momoko; Boutin, Thibaud S.; Magi, 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; Maerz, 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, Noel 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.; Gayan, 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.; Sparso, 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; Blueher, 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; Franberg, 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. 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Chen, J., Spracklen, C.N., Marenne, G. et al. The trans-ancestral genomic architecture of glycemic traits. Nat Genet 53, 840–860 (2021). https://doi.org/10.1038/s41588-021-00852-9
© The Author(s), under exclusive licence to Springer Nature America, Inc. 2021. This is a post-peer-review, pre-copyedit version of an article published in Nat Genet. The final authenticated version is available online at https://doi.org/10.1038/s41588-021-00852-9.
https://rightsstatements.org/vocab/InC/1.0/
https://urn.fi/URN:NBN:fi-fe2022030422054
Tiivistelmä
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 x 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.
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Nature : 7890 (Springer Nature, 09.12.2021) -
Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices
Natarajan, Pradeep; Pampana, Akhil; Graham, Sarah E.; Ruotsalainen, Sanni E.; Perry, James A.; de Vries, Paul S.; Broome, Jai G.; Pirruccello, James P.; Honigbere, Michael C.; Aragam, Krishna; Wolford, Brooke; Brody, Jennifer A.; Antonacci-Fulton, Lucinda; Arden, Moscati; Aslibekyan, Stella; Assimes, Themistocles L.; Ballantyne, Christie M.; Bielak, Lawrence F.; Bisl, Joshua C.; Cade, Brian E.; Do, Ron; Doddapaneni, Harsha; Emery, Leslie S.; Hung, Yi-Jen; Irvin, Marguerite R.; Khan, Alyna T.; Lange, Leslie; Lee, Jiwon; Lemaitre, Rozenn N.; Martin, Lisa W.; Metcalf, Ginger; Montasser, May E.; Moon, Jee-Young; Muzny, Donna; Connell, Jeffrey R. 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Nature communications : 1 (Springer Nature, 12.04.2021)