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. Craig; Jorgensen, Marit E.; Joshi, Peter K.; Kalyani, Rita R.; Kandeel, Fouad R.; Katsuya, Tomohiro; Khor, Chiea Chuen; Kiess, Wieland; Kolcic, Ivana; Kuulasmaa, Teemu; Kuusisto, Johanna; Lall, Kristi; Lam, Kelvin; Lawlor, Deborah A.; Lee, Nanette R.; Lemaitre, Rozenn N.; Li, Honglan; Lin, Shih-Yi; Lindstrom, 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; Schuermann, 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, Goncalo R.; Adair, Linda S.; Aguilar-Salinas, Carlos Alberto; Alarcon-Riquelme, Marta E.; An, Ping; Aviles-Santa, Larissa; Becker, Diane M.; Beilin, Lawrence J.; Bergmann, Sven; Bisgaard, Hans; Black, Corri; Boehnke, Michael; Boerwinkle, Eric; Boehm, Bernhard O.; Bonnelykke, Klaus; Boomsma, D. I.; Bottinger, Erwin P.; Buchanan, Thomas A.; Canouil, Mickael; 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; Elmstahl, Solve; 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.; Järvelin, 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.; Koerner, 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.; Njolstad, 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; Sorensen, Thorkild I. A.; Spector, Tim D.; Stanton, Alice; Steves, Claire J.; Stumvoll, Michael; Sun, Liang; Tabara, Yasuharu; Tai, E. Shyong; Timpson, Nicholas J.; Tonjes, 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, Loic; Yokota, Mitsuhiro; Zeggini, Eleftheria; Zheng, Wei; Zonderman, Alan B.; Rotter, Jerome I.; Gloyn, Anna L.; McCarthy, Mark I.; Dupuis, Josee; 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, Ines (2021-05-31)
 
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URL:
https://doi.org/10.1038/s41588-021-00852-9

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. Craig
Jorgensen, Marit E.
Joshi, Peter K.
Kalyani, Rita R.
Kandeel, Fouad R.
Katsuya, Tomohiro
Khor, Chiea Chuen
Kiess, Wieland
Kolcic, Ivana
Kuulasmaa, Teemu
Kuusisto, Johanna
Lall, Kristi
Lam, Kelvin
Lawlor, Deborah A.
Lee, Nanette R.
Lemaitre, Rozenn N.
Li, Honglan
Lin, Shih-Yi
Lindstrom, 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
Schuermann, 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, Goncalo R.
Adair, Linda S.
Aguilar-Salinas, Carlos Alberto
Alarcon-Riquelme, Marta E.
An, Ping
Aviles-Santa, Larissa
Becker, Diane M.
Beilin, Lawrence J.
Bergmann, Sven
Bisgaard, Hans
Black, Corri
Boehnke, Michael
Boerwinkle, Eric
Boehm, Bernhard O.
Bonnelykke, Klaus
Boomsma, D. I.
Bottinger, Erwin P.
Buchanan, Thomas A.
Canouil, Mickael
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
Elmstahl, Solve
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.
Järvelin, 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.
Koerner, 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.
Njolstad, 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
Sorensen, Thorkild I. A.
Spector, Tim D.
Stanton, Alice
Steves, Claire J.
Stumvoll, Michael
Sun, Liang
Tabara, Yasuharu
Tai, E. Shyong
Timpson, Nicholas J.
Tonjes, 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, Loic
Yokota, Mitsuhiro
Zeggini, Eleftheria
Zheng, Wei
Zonderman, Alan B.
Rotter, Jerome I.
Gloyn, Anna L.
McCarthy, Mark I.
Dupuis, Josee
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, Ines
Springer Nature
31.05.2021

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

https://rightsstatements.org/vocab/InC/1.0/
© 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/
doi:https://doi.org/10.1038/s41588-021-00852-9
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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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