The Trans-Ancestral Genomic Architecture of Glycemic Traits

Citation

Chen, Ji; Spracklen, Cassandra N.; Marenne, Gaëlle; Varshney, Arushi; Corbin, Laura J.; Luan, Jian'an; Willems, Sara M.; Wu, Ying; Zhang, Xiaoshuai; & Horikoshi, Momoko, et al. (2021). The Trans-Ancestral Genomic Architecture of Glycemic Traits. Nature Genetics, 53(6), 840-860. PMCID: PMC7610958

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.

URL

http://dx.doi.org/10.1038/s41588-021-00852-9

Reference Type

Journal Article

Year Published

2021

Journal Title

Nature Genetics

Author(s)

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
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 R.
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 N.
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 H.
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 H.
Raffield, Laura
Torvik, Laura J.
Rich, Stephen S.
Robertson, Neil R.
Rueedi, Rico
Ryan, Kathleen A.
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 H.
Zhao, Jing-Hua
Zhao, Wei
Amin, Najaf
Arzumanyan, Zorayr
Astrup, Arne
Bakker, Stephan J. L.
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Beekman, Marian
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Campbell, Archie
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Chang, Yi-Cheng
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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 P.
Moon, Sanghoon
Nabika, Toru
Nadkarni, Girish
Nadler, Jerry L.
Nelis, Mari
Neville, Matt
Norris, Jill M.
Ohyagi, Yasumasa
Peters, Annette
Peyser, Patricia A.
Polasek, Ozren
Qi, Qibin
Raven, Dennis
Reilly, Dermot F.
Reiner, Alex P.
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 H.
Timmers, Paul R. H. J.
Tremoli, Elena
Tsai, Michael Y.
Uitterlinden, Andre G.
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 A.
Alarcón-Riquelme, Marta E.
An, Ping
Aviles-Santa, M. Larissa
Becker, Diane M.
Beilin, Lawrence J.
Bergmann, Sven
Bisgaard, Hans
Black, Corri
Boehnke, Michael
Boerwinkle, Eric A.
Böhm, Bernhard O.
Bønnelykke, Klaus
Boomsma, Dorret I.
Bottinger, Erwin P.
Buchanan, Thomas A.
Canouil, Mickaël
Caulfield, Mark J.
Chambers, John C.
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Chen, Yii-Der Ida
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de Silva, H. Janaka
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Grallert, Harald
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Grimsgaard, Sameline
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Hamsten, Anders
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Leander, Karin
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Lindgren, Cecilia M.
Liu, Simin
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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 S.
Ridker, Paul M.
Rosendaal, Frits R.
Saaristo, Timo E.
Sandhu, Manjinder S.
Saramies, Jouko
Schneiderman, Neil
Schwarz, Peter E. H.
Scott, Laura J.
Selvin, Elizabeth
Sever, Peter
Shu, Xiao-Ou
Slagboom, P. E.
Small, Kerrin S.
Smith, Blair H.
Snieder, Harold
Sofer, Tamar
Sørensen, Thorkild I. A.
Spector, Tim D.
Stanton, Alice V.
Steves, Claire J.
Stumvoll, Michael
Sun, Liang
Tabara, Yasuharu
Tai, E. S.
Timpson, Nicholas J.
Tönjes, Anke
Tuomilehto, Jaakko
Tusie, Teresa
Uusitupa, Matti
van der Harst, Pim
van Duijn, Cornelia M.
Vitart, Veronique
Vollenweider, Peter
Vrijkotte, Tanja G. M.
Wagenknecht, Lynne E.
Walker, Mark
Wang, Y. X.
Wareham, Nick J.
Watanabe, Richard M.
Watkins, Hugh
Wei, Wen Bin
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

Article Type

Regular

PMCID

PMC7610958

ORCiD

Adair - 0000-0002-3670-8073
Gordon-Larsen - 0000-0001-5322-4188
Du - 0000-0003-1156-0866