The trans-ancestral genomic architecture of glycemic traits.
Chen, Ji; Spracklen, Cassandra N; Marenne, Gaëlle
; Varshney, Arushi; Corbin, Laura J; Luan, Jian'an; Willems, Sara M; Wu, Ying; Zhang, Xiaoshuai; Horikoshi, Momoko; +397 more...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 VR; 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 JL; 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 JC; 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, 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 RHJ; 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, DI; 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 LR; 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 JF; Magnusson, Patrik KE; 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 NA; 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 IA; 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 GM; 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 CJ; Mohlke, Karen L; Langenberg, Claudia; Wheeler, Eleanor; Morris, Andrew P; Barroso, Inês; and Meta-Analysis of Glucose and Insulin-related Traits Consortium (
(2021)
The trans-ancestral genomic architecture of glycemic traits.
Nature genetics, 53 (6).
pp. 840-860.
ISSN 1061-4036
DOI: 10.1038/s41588-021-00852-9
; Varshney, Arushi; Corbin, Laura J; Luan, Jian'an; Willems, Sara M; Wu, Ying; Zhang, Xiaoshuai; Horikoshi, Momoko; +397 more...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 VR; 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 JL; 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 JC; 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, 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 RHJ; 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, DI; 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 LR; 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 JF; Magnusson, Patrik KE; 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 NA; 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 IA; 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 GM; 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 CJ; Mohlke, Karen L; Langenberg, Claudia; Wheeler, Eleanor; Morris, Andrew P; Barroso, Inês; and Meta-Analysis of Glucose and Insulin-related Traits Consortium (
(2021)
The trans-ancestral genomic architecture of glycemic traits.
Nature genetics, 53 (6).
pp. 840-860.
ISSN 1061-4036
DOI: 10.1038/s41588-021-00852-9
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.
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subject - Accepted Version
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error - This is an author accepted manuscript version of an article accepted for publication, and following peer review. Please be aware that minor differences may exist between this version and the final version if you wish to cite from it.
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