The trans-ancestral genomic architecture of glycemic traits

Chen, J.; Spracklen, C.N.; Marenne, G.; Varshney, A.; Corbin, L.J.; Luan, J.; Willems, S.M.; Ying, W.; Zhang, X.; Horikoshi, M.; Boutin, T.S.; Mägi, R.; Waage, J.; Li-Gao, R.; Chan, K.H.K.; Yao, J.; Anasanti, M.D.; Chu, A.Y.; Claringbould, A.; Heikkinen, J.; Hong, J.; Hottenga, J.; Huo, S.; Kaakinen, M.A.; Louie, T.; März, W.; Moreno-Macias, H.; Ndungu, A.; Nelson, S.C.; Nolte, I.M.; North, K.E.; Raulerson, C.K.; Ray, D.; Rohde, R.; Rybin, D.; Schurmann, C.; Sim, X.; Southam, L.; Stewart, I.D.; Wang, C.A.; Wang, Y.; Peitao, W.; Zhang, W.; Ahluwalia, T.S.; Appel, E.V.R.; Bielak, L.F.; Brody, J.A.; Burtt, N.P.; Cabrera, C.P.; Cade, B.E.; Chai, J.F.; Chai, X.; Chang, L.; Chen, C.; Chen, B.H.; Chitrala, K.N.; Chiu, Y.; de Haan, H.G.; Delgado, G.E.; Demirkan, A.; Duan, Q.; Engmann, J.; Fatumo, S.A.; Gayán, J.; Giulianini, F.; Gong, J.H.; Gustafsson, S.; Hai, Y.; Hartwig, F.P.; Jing, H.; Heianza, Y.; Huang, T.; Huerta-Chagoya, A.; Hwang, M.Y.; Jensen, R.A.; Kawaguchi, T.; Kentistou, K.A.; Kim, Y.J.; Kleber, M.E.; Kooner, I.K.; Lai, S.; Lange, L.A.; Langefeld, C.D.; Lauzon, M.; Man, L.; Ligthart, S.; Liu, J.; Loh, M.; Long, J.; Lyssenko, V.; Mangino, M.; Marzi, C.; Montasser, M.E.; Nag, A.; Nakatochi, M.; Noce, D.; Noordam, R.; Pistis, G.; Preuss, M.; Raffield, L.; Rasmussen-Torvik, L.J.; Rich, S.S.; Robertson, N.R.; Rueedi, R.; Ryan, K.; Sanna, S.; Saxena, R.; Schraut, K.E.; Sennblad, B.; Setoh, K.; Smith, A.V.; Sparsø, T.; Strawbridge, R.J.; Takeuchi, F.; Tan, J.; Trompet, S.; van den Akker, E.; van der Most, P.J.; Verweij, N.; Vogel, M.; Wang, H.; Wang, C.; Wang, N.; Warren, H.R.; Wen, W.; Wilsgaard, T.; Wong, A.; Wood, A.R.; Xie, T.; Zafarmand, M.H.; Zhao, J.; Zhao, W.; Amin, N.; Arzumanyan, Z.; Astrup, A.; Bakker, S.J.L.; Baldassarre, D.; Beekman, M.; Bergman, R.N.; Bertoni, A.; Blüher, M.; Bonnycastle, L.L.; Bornstein, S.R.; Bowden, D.W.; Cai, Q.; Campbell, A.; Campbell, H.; Chang, Y.C.; de Geus, E.J.C.; Dehghan, A.; Shufa, D.; Eiriksdottir, G.; Farmaki, A.E.; Frånberg, M.; Fuchsberger, C.; Gao, Y.; Gjesing, A.P.; Goel, A.; Han, S.; Hartman, C.A.; Herder, C.; Hicks, A.A.; Hsieh, C.; Hsueh, W.A.; Ichihara, S.; Igase, M.; Ikram, M.A.; Johnson, W.C.; Jørgensen, M.E.; Joshi, P.K.; Kalyani, R.R.; Kandeel, F.R.; Katsuya, T.; Khor, C.C.; Kiess, W.; Kolcic, I.; Kuulasmaa, T.; Kuusisto, J.; Läll, K.; Lam, K.; Lawlor, D.A.; Lee, N.R.; Lemaitre, R.N.; Honglan, L.; Lin, S.; Lindström, J.; Linneberg, A.; Liu, J.; Lorenzo, C.; Matsubara, T.; Matsuda, F.; Mingrone, G.; Mooijaart, S.; Moon, S.; Nabika, T.; Nadkarni, G.N.; Nadler, J.L.; Nelis, M.; Neville, M.J.; Norris, J.M.; Ohyagi, Y.; Peters, A.; Peyser, P.A.; Polasek, O.; Qibin, Q.; Raven, D.; Reilly, D.F.; Reiner, A.; Rivideneira, F.; Roll, K.; Rudan, I.; Sabanayagam, C.; Sandow, K.; Sattar, N.; Schürmann, A.; Shi, J.; Stringham, H.M.; Taylor, K.D.; Teslovich, T.M.; Thuesen, B.; Timmers, P.R.H.J.; Tremoli, E.; Tsai, M.Y.; Uitterlinden, A.; van Dam, R.M.; van Heemst, D.; van Hylckama Vlieg, A.; van Vliet-Ostaptchouk, J.V.; Vangipurapu, J.; Vestergaard, H.; Wang, T.; Willems van Dijk, K.; Zemunik, T.; Abecasis, G.R.; Adair, L.S.; Aguilar-Salinas, C.A.; Alarcón-Riquelme, M.E.; Ping, A.; Aviles-Santa, L.; Becker, D.M.; Beilin, L.J.; Bergmann, S.; Bisgaard, H.; Black, C.; Boehnke, M.; Boerwinkle, E.; Böhm, B.O.; Bønnelykke, K.; Boomsma, D.I.; Bottinger, E.P.; Buchanan, T.A.; Canouil, M.; Caulfield, M.J.; Chambers, J.C.; Chasman, D.I.; Chen, Y.I.; Cheng, C.; Collins, F.S.; Correa, A.; Cucca, F.; de Silva, H.J.; Dedoussis, G.; Elmståhl, S.; Evans, M.K.; Ferrannini, E.; Ferrucci, L.; Florez, J.C.; Franks, P.W.; Frayling, T.M.; Froguel, P.; Gigante, B.; Goodarzi, M.O.; Gordon-Larsen, P.; Grallert, H.; Grarup, N.; Grimsgaard, S.; Groop, L.; Gudnason, V.; Guo, X.; Hamsten, A.; Hansen, T.; Hayward, C.; Heckbert, S.R.; Horta, B.L.; Huang, W.; Ingelsson, E.; James, P.S.; Jarvelin, M.; Jonas, J.B.; Jukema, J.W.; Kaleebu, P.; Kaplan, R.; Kardia, S.L.R.; Kato, N.; Keinanen-Kiukaanniemi, S.M.; Kim, B.; Kivimaki, M.; Koistinen, H.A.; Kooner, J.S.; Körner, A.; Kovacs, P.; Kuh, D.; Kumari, M.; Kutalik, Z.; Laakso, M.; Lakka, T.A.; Launer, L.J.; Leander, K.; Huaixing, L.; Lin, X.; Lind, L.; Lindgren, C.; Liu, S.; Loos, R.J.F.; Magnusson, P.K.E.; Mahajan, A.; Metspalu, A.; Mook-Kanamori, D.O.; Mori, T.A.; Munroe, P.B.; Njølstad, I.; O'Connell, J.R.; Oldehinkel, A.J.; Ong, K.K.; Padmanabhan, S.; Palmer, C.N.A.; Palmer, N.D.; Pedersen, O.; Pennell, C.E.; Porteous, D.J.; Pramstaller, P.P.; Province, M.A.; Psaty, B.M.; Lu, Q.; Raffel, L.J.; Rauramaa, R.; Redline, S.; Ridker, P.M.; Rosendaal, F.R.; Saaristo, T.E.; Sandhu, M.; Saramies, J.; Schneiderman, N.; Schwarz, P.; Scott, L.J.; Selvin, E.; Sever, P.; Shu, X.; Slagboom, P.E.; Small, K.S.; Smith, B.H.; Snieder, H.; Sofer, T.; Sørensen, T.I.A.; Spector, T.D.; Stanton, A.; Steves, C.J.; Stumvoll, M.; Sun, L.; Tabara, Y.; Tai, E.S.; Timpson, N.J.; Tönjes, A.; Tuomilehto, J.; Tusie, T.; Uusitupa, M.; van der Harst, P.; van Duijn, C.; Vitart, V.; Vollenweider, P.; Vrijkotte, T.G.M.; Wagenknecht, L.E.; Walker, M.; Wang, Y.X.; Wareham, N.J.; Watanabe, R.M.; Watkins, H.; Wei, W.B.; Wickremasinghe, A.R.; Willemsen, G.; Wilson, J.F.; Wong, T.; Jer-Yuarn, W.; Xiang, A.H.; Yanek, L.R.; Yengo, L.; Yokota, M.; Zeggini, E.; Zheng, W.; Zonderman, A.B.; Rotter, J.I.; Gloyn, A.L.; Mccarthy, M.I.; Dupuis, J.; Meigs, J.B.; Scott, R.A.; Prokopenko, I.; Leong, A.; Liu, C.; Parker, S.C.J.; Mohlke, K.L.; Langenberg, C.; Wheeler, E.; Morris, A.P.; Barroso, I.

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.

The trans-ancestral genomic architecture of glycemic traits / J. Chen, C.N. Spracklen, G. Marenne, A. Varshney, L.J. Corbin, J. Luan, S.M. Willems, Y. Wu, X. Zhang, M. Horikoshi, T.S. Boutin, R. Mägi, J. Waage, R. Li-Gao, K.H.K. Chan, J. Yao, M.D. Anasanti, A.Y. Chu, A. Claringbould, J. Heikkinen, J. Hong, J. Hottenga, S. Huo, M.A. Kaakinen, T. Louie, W. März, H. Moreno-Macias, A. Ndungu, S.C. Nelson, I.M. Nolte, K.E. North, C.K. Raulerson, D. Ray, R. Rohde, D. Rybin, C. Schurmann, X. Sim, L. Southam, I.D. Stewart, C.A. Wang, Y. Wang, P. Wu, W. Zhang, T.S. Ahluwalia, E.V.R. Appel, L.F. Bielak, J.A. Brody, N.P. Burtt, C.P. Cabrera, B.E. Cade, J.F. Chai, X. Chai, L. Chang, C. Chen, B.H. Chen, K.N. Chitrala, Y. Chiu, H.G. de Haan, G.E. Delgado, A. Demirkan, Q. Duan, J. Engmann, S.A. Fatumo, J. Gayán, F. Giulianini, J.H. Gong, S. Gustafsson, Y. Hai, F.P. Hartwig, J. He, Y. Heianza, T. Huang, A. Huerta-Chagoya, M.Y. Hwang, R.A. Jensen, T. Kawaguchi, K.A. Kentistou, Y.J. Kim, M.E. Kleber, I.K. Kooner, S. Lai, L.A. Lange, C.D. Langefeld, M. Lauzon, M. Li, S. Ligthart, J. Liu, M. Loh, J. Long, V. Lyssenko, M. Mangino, C. Marzi, M.E. Montasser, A. Nag, M. Nakatochi, D. Noce, R. Noordam, G. Pistis, M. Preuss, L. Raffield, L.J. Rasmussen-Torvik, S.S. Rich, N.R. Robertson, R. Rueedi, K. Ryan, S. Sanna, R. Saxena, K.E. Schraut, B. Sennblad, K. Setoh, A.V. Smith, T. Sparsø, R.J. Strawbridge, F. Takeuchi, J. Tan, S. Trompet, E. van den Akker, P.J. van der Most, N. Verweij, M. Vogel, H. Wang, C. Wang, N. Wang, H.R. Warren, W. Wen, T. Wilsgaard, A. Wong, A.R. Wood, T. Xie, M.H. Zafarmand, J. Zhao, W. Zhao, N. Amin, Z. Arzumanyan, A. Astrup, S.J.L. Bakker, D. Baldassarre, M. Beekman, R.N. Bergman, A. Bertoni, M. Blüher, L.L. Bonnycastle, S.R. Bornstein, D.W. Bowden, Q. Cai, A. Campbell, H. Campbell, Y.C. Chang, E.J.C. de Geus, A. Dehghan, S. Du, G. Eiriksdottir, A.E. Farmaki, M. Frånberg, C. Fuchsberger, Y. Gao, A.P. Gjesing, A. Goel, S. Han, C.A. Hartman, C. Herder, A.A. Hicks, C. Hsieh, W.A. Hsueh, S. Ichihara, M. Igase, M.A. Ikram, W.C. Johnson, M.E. Jørgensen, P.K. Joshi, R.R. Kalyani, F.R. Kandeel, T. Katsuya, C.C. Khor, W. Kiess, I. Kolcic, T. Kuulasmaa, J. Kuusisto, K. Läll, K. Lam, D.A. Lawlor, N.R. Lee, R.N. Lemaitre, H. Li, S. Lin, J. Lindström, A. Linneberg, J. Liu, C. Lorenzo, T. Matsubara, F. Matsuda, G. Mingrone, S. Mooijaart, S. Moon, T. Nabika, G.N. Nadkarni, J.L. Nadler, M. Nelis, M.J. Neville, J.M. Norris, Y. Ohyagi, A. Peters, P.A. Peyser, O. Polasek, Q. Qi, D. Raven, D.F. Reilly, A. Reiner, F. Rivideneira, K. Roll, I. Rudan, C. Sabanayagam, K. Sandow, N. Sattar, A. Schürmann, J. Shi, H.M. Stringham, K.D. Taylor, T.M. Teslovich, B. Thuesen, P.R.H.J. Timmers, E. Tremoli, M.Y. Tsai, A. Uitterlinden, R.M. van Dam, D. van Heemst, A. van Hylckama Vlieg, J.V. van Vliet-Ostaptchouk, J. Vangipurapu, H. Vestergaard, T. Wang, K. Willems van Dijk, T. Zemunik, G.R. Abecasis, L.S. Adair, C.A. Aguilar-Salinas, M.E. Alarcón-Riquelme, P. An, L. Aviles-Santa, D.M. Becker, L.J. Beilin, S. Bergmann, H. Bisgaard, C. Black, M. Boehnke, E. Boerwinkle, B.O. Böhm, K. Bønnelykke, D.I. Boomsma, E.P. Bottinger, T.A. Buchanan, M. Canouil, M.J. Caulfield, J.C. Chambers, D.I. Chasman, Y.I. Chen, C. Cheng, F.S. Collins, A. Correa, F. Cucca, H.J. de Silva, G. Dedoussis, S. Elmståhl, M.K. Evans, E. Ferrannini, L. Ferrucci, J.C. Florez, P.W. Franks, T.M. Frayling, P. Froguel, B. Gigante, M.O. Goodarzi, P. Gordon-Larsen, H. Grallert, N. Grarup, S. Grimsgaard, L. Groop, V. Gudnason, X. Guo, A. Hamsten, T. Hansen, C. Hayward, S.R. Heckbert, B.L. Horta, W. Huang, E. Ingelsson, P.S. James, M. Jarvelin, J.B. Jonas, J.W. Jukema, P. Kaleebu, R. Kaplan, S.L.R. Kardia, N. Kato, S.M. Keinanen-Kiukaanniemi, B. Kim, M. Kivimaki, H.A. Koistinen, J.S. Kooner, A. Körner, P. Kovacs, D. Kuh, M. Kumari, Z. Kutalik, M. Laakso, T.A. Lakka, L.J. Launer, K. Leander, H. Li, X. Lin, L. Lind, C. Lindgren, S. Liu, R.J.F. Loos, P.K.E. Magnusson, A. Mahajan, A. Metspalu, D.O. Mook-Kanamori, T.A. Mori, P.B. Munroe, I. Njølstad, J.R. O'Connell, A.J. Oldehinkel, K.K. Ong, S. Padmanabhan, C.N.A. Palmer, N.D. Palmer, O. Pedersen, C.E. Pennell, D.J. Porteous, P.P. Pramstaller, M.A. Province, B.M. Psaty, L. Qi, L.J. Raffel, R. Rauramaa, S. Redline, P.M. Ridker, F.R. Rosendaal, T.E. Saaristo, M. Sandhu, J. Saramies, N. Schneiderman, P. Schwarz, L.J. Scott, E. Selvin, P. Sever, X. Shu, P.E. Slagboom, K.S. Small, B.H. Smith, H. Snieder, T. Sofer, T.I.A. Sørensen, T.D. Spector, A. Stanton, C.J. Steves, M. Stumvoll, L. Sun, Y. Tabara, E.S. Tai, N.J. Timpson, A. Tönjes, J. Tuomilehto, T. Tusie, M. Uusitupa, P. van der Harst, C. van Duijn, V. Vitart, P. Vollenweider, T.G.M. Vrijkotte, L.E. Wagenknecht, M. Walker, Y.X. Wang, N.J. Wareham, R.M. Watanabe, H. Watkins, W.B. Wei, A.R. Wickremasinghe, G. Willemsen, J.F. Wilson, T. Wong, J. Wu, A.H. Xiang, L.R. Yanek, L. Yengo, M. Yokota, E. Zeggini, W. Zheng, A.B. Zonderman, J.I. Rotter, A.L. Gloyn, M.I. Mccarthy, J. Dupuis, J.B. Meigs, R.A. Scott, I. Prokopenko, A. Leong, C. Liu, S.C.J. Parker, K.L. Mohlke, C. Langenberg, E. Wheeler, A.P. Morris, I. Barroso. - In: NATURE GENETICS. - ISSN 1061-4036. - (2021). [Epub ahead of print] [10.1038/s41588-021-00852-9]

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;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;D. Baldassarre^{Membro del Collaboration Group};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;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 R H J;E. Tremoli^{Membro del Collaboration Group};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, D I;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 L R;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 J F;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;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 I A;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 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, 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

2021

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.

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	Presenza di coautori internazionali
	
			Sì
		
	Lingua dell'articolo
	
			English
		
	Settori scientifico-disciplinari dell'articolo
	
			Settore BIO/14 - Farmacologia
		
	Tipo
	
			Articolo
		
	Revisione (peer review)
	
			Esperti anonimi
		
	Classificazione in base al tipo di ricerca
	
			Ricerca applicata
		
	Classificazione della pubblicazione
	
			Pubblicazione scientifica
		
	Data di pubblicazione
	
			2021
		
	Data ahead of print o data di stampa
	
			31-mag-2021
		
	Rivista in ANCE
	
			NATURE GENETICS
		
	Stato di pubblicazione
	
			Epub ahead of print
		
	Rilevanza del periodico
	
			Periodico con rilevanza internazionale
		
	DOI
	
			https://dx.doi.org/10.1038/s41588-021-00852-9
		
	Banca dati sorgente
	
			pubmed
crossref
		
	Identificativo ISI
	
			WOS:000656384400001
		
	Identificativo SCOPUS
	
			2-s2.0-85108020584
		
	Identificativo PUBMED
	
			34059833
		
	Adesione alla policy Open Access di Ateneo
	
			Aderisco
		
	Tipologia
	
			info:eu-repo/semantics/article
		
	Citazione
	
			The trans-ancestral genomic architecture of glycemic traits / J. Chen, C.N. Spracklen, G. Marenne, A. Varshney, L.J. Corbin, J. Luan, S.M. Willems, Y. Wu, X. Zhang, M. Horikoshi, T.S. Boutin, R. Mägi, J. Waage, R. Li-Gao, K.H.K. Chan, J. Yao, M.D. Anasanti, A.Y. Chu, A. Claringbould, J. Heikkinen, J. Hong, J. Hottenga, S. Huo, M.A. Kaakinen, T. Louie, W. März, H. Moreno-Macias, A. Ndungu, S.C. Nelson, I.M. Nolte, K.E. North, C.K. Raulerson, D. Ray, R. Rohde, D. Rybin, C. Schurmann, X. Sim, L. Southam, I.D. Stewart, C.A. Wang, Y. Wang, P. Wu, W. Zhang, T.S. Ahluwalia, E.V.R. Appel, L.F. Bielak, J.A. Brody, N.P. Burtt, C.P. Cabrera, B.E. Cade, J.F. Chai, X. Chai, L. Chang, C. Chen, B.H. Chen, K.N. Chitrala, Y. Chiu, H.G. de Haan, G.E. Delgado, A. Demirkan, Q. Duan, J. Engmann, S.A. Fatumo, J. Gayán, F. Giulianini, J.H. Gong, S. Gustafsson, Y. Hai, F.P. Hartwig, J. He, Y. Heianza, T. Huang, A. Huerta-Chagoya, M.Y. Hwang, R.A. Jensen, T. Kawaguchi, K.A. Kentistou, Y.J. Kim, M.E. Kleber, I.K. Kooner, S. Lai, L.A. Lange, C.D. Langefeld, M. Lauzon, M. Li, S. Ligthart, J. Liu, M. Loh, J. Long, V. Lyssenko, M. Mangino, C. Marzi, M.E. Montasser, A. Nag, M. Nakatochi, D. Noce, R. Noordam, G. Pistis, M. Preuss, L. Raffield, L.J. Rasmussen-Torvik, S.S. Rich, N.R. Robertson, R. Rueedi, K. Ryan, S. Sanna, R. Saxena, K.E. Schraut, B. Sennblad, K. Setoh, A.V. Smith, T. Sparsø, R.J. Strawbridge, F. Takeuchi, J. Tan, S. Trompet, E. van den Akker, P.J. van der Most, N. Verweij, M. Vogel, H. Wang, C. Wang, N. Wang, H.R. Warren, W. Wen, T. Wilsgaard, A. Wong, A.R. Wood, T. Xie, M.H. Zafarmand, J. Zhao, W. Zhao, N. Amin, Z. Arzumanyan, A. Astrup, S.J.L. Bakker, D. Baldassarre, M. Beekman, R.N. Bergman, A. Bertoni, M. Blüher, L.L. Bonnycastle, S.R. Bornstein, D.W. Bowden, Q. Cai, A. Campbell, H. Campbell, Y.C. Chang, E.J.C. de Geus, A. Dehghan, S. Du, G. Eiriksdottir, A.E. Farmaki, M. Frånberg, C. Fuchsberger, Y. Gao, A.P. Gjesing, A. Goel, S. Han, C.A. Hartman, C. Herder, A.A. Hicks, C. Hsieh, W.A. Hsueh, S. Ichihara, M. Igase, M.A. Ikram, W.C. Johnson, M.E. Jørgensen, P.K. Joshi, R.R. Kalyani, F.R. Kandeel, T. Katsuya, C.C. Khor, W. Kiess, I. Kolcic, T. Kuulasmaa, J. Kuusisto, K. Läll, K. Lam, D.A. Lawlor, N.R. Lee, R.N. Lemaitre, H. Li, S. Lin, J. Lindström, A. Linneberg, J. Liu, C. Lorenzo, T. Matsubara, F. Matsuda, G. Mingrone, S. Mooijaart, S. Moon, T. Nabika, G.N. Nadkarni, J.L. Nadler, M. Nelis, M.J. Neville, J.M. Norris, Y. Ohyagi, A. Peters, P.A. Peyser, O. Polasek, Q. Qi, D. Raven, D.F. Reilly, A. Reiner, F. Rivideneira, K. Roll, I. Rudan, C. Sabanayagam, K. Sandow, N. Sattar, A. Schürmann, J. Shi, H.M. Stringham, K.D. Taylor, T.M. Teslovich, B. Thuesen, P.R.H.J. Timmers, E. Tremoli, M.Y. Tsai, A. Uitterlinden, R.M. van Dam, D. van Heemst, A. van Hylckama Vlieg, J.V. van Vliet-Ostaptchouk, J. Vangipurapu, H. Vestergaard, T. Wang, K. Willems van Dijk, T. Zemunik, G.R. Abecasis, L.S. Adair, C.A. Aguilar-Salinas, M.E. Alarcón-Riquelme, P. An, L. Aviles-Santa, D.M. Becker, L.J. Beilin, S. Bergmann, H. Bisgaard, C. Black, M. Boehnke, E. Boerwinkle, B.O. Böhm, K. Bønnelykke, D.I. Boomsma, E.P. Bottinger, T.A. Buchanan, M. Canouil, M.J. Caulfield, J.C. Chambers, D.I. Chasman, Y.I. Chen, C. Cheng, F.S. Collins, A. Correa, F. Cucca, H.J. de Silva, G. Dedoussis, S. Elmståhl, M.K. Evans, E. Ferrannini, L. Ferrucci, J.C. Florez, P.W. Franks, T.M. Frayling, P. Froguel, B. Gigante, M.O. Goodarzi, P. Gordon-Larsen, H. Grallert, N. Grarup, S. Grimsgaard, L. Groop, V. Gudnason, X. Guo, A. Hamsten, T. Hansen, C. Hayward, S.R. Heckbert, B.L. Horta, W. Huang, E. Ingelsson, P.S. James, M. Jarvelin, J.B. Jonas, J.W. Jukema, P. Kaleebu, R. Kaplan, S.L.R. Kardia, N. Kato, S.M. Keinanen-Kiukaanniemi, B. Kim, M. Kivimaki, H.A. Koistinen, J.S. Kooner, A. Körner, P. Kovacs, D. Kuh, M. Kumari, Z. Kutalik, M. Laakso, T.A. Lakka, L.J. Launer, K. Leander, H. Li, X. Lin, L. Lind, C. Lindgren, S. Liu, R.J.F. Loos, P.K.E. Magnusson, A. Mahajan, A. Metspalu, D.O. Mook-Kanamori, T.A. Mori, P.B. Munroe, I. Njølstad, J.R. O'Connell, A.J. Oldehinkel, K.K. Ong, S. Padmanabhan, C.N.A. Palmer, N.D. Palmer, O. Pedersen, C.E. Pennell, D.J. Porteous, P.P. Pramstaller, M.A. Province, B.M. Psaty, L. Qi, L.J. Raffel, R. Rauramaa, S. Redline, P.M. Ridker, F.R. Rosendaal, T.E. Saaristo, M. Sandhu, J. Saramies, N. Schneiderman, P. Schwarz, L.J. Scott, E. Selvin, P. Sever, X. Shu, P.E. Slagboom, K.S. Small, B.H. Smith, H. Snieder, T. Sofer, T.I.A. Sørensen, T.D. Spector, A. Stanton, C.J. Steves, M. Stumvoll, L. Sun, Y. Tabara, E.S. Tai, N.J. Timpson, A. Tönjes, J. Tuomilehto, T. Tusie, M. Uusitupa, P. van der Harst, C. van Duijn, V. Vitart, P. Vollenweider, T.G.M. Vrijkotte, L.E. Wagenknecht, M. Walker, Y.X. Wang, N.J. Wareham, R.M. Watanabe, H. Watkins, W.B. Wei, A.R. Wickremasinghe, G. Willemsen, J.F. Wilson, T. Wong, J. Wu, A.H. Xiang, L.R. Yanek, L. Yengo, M. Yokota, E. Zeggini, W. Zheng, A.B. Zonderman, J.I. Rotter, A.L. Gloyn, M.I. Mccarthy, J. Dupuis, J.B. Meigs, R.A. Scott, I. Prokopenko, A. Leong, C. Liu, S.C.J. Parker, K.L. Mohlke, C. Langenberg, E. Wheeler, A.P. Morris, I. Barroso. - In: NATURE GENETICS. - ISSN 1061-4036. - (2021). [Epub ahead of print] [10.1038/s41588-021-00852-9]
		
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			Prodotti della ricerca::01 - Articolo su periodico
		
	Numero autori
	
			405
		
	Tipologia sito docente
	
			262
		
	Tipologia
	
			Article (author)
		
	Presenza impact factor
	
			Periodico con Impact Factor
		
	Tutti gli autori
	
			J. Chen, C.N. Spracklen, G. Marenne, A. Varshney, L.J. Corbin, J. Luan, S.M. Willems, Y. Wu, X. Zhang, M. Horikoshi, T.S. Boutin, R. Mägi, J. Waage, R. Li-Gao, K.H.K. Chan, J. Yao, M.D. Anasanti, A.Y. Chu, A. Claringbould, J. Heikkinen, J. Hong, J. Hottenga, S. Huo, M.A. Kaakinen, T. Louie, W. März, H. Moreno-Macias, A. Ndungu, S.C. Nelson, I.M. Nolte, K.E. North, C.K. Raulerson, D. Ray, R. Rohde, D. Rybin, C. Schurmann, X. Sim, L. Southam, I.D. Stewart, C.A. Wang, Y. Wang, P. Wu, W. Zhang, T.S. Ahluwalia, E.V.R. Appel, L.F. Bielak, J.A. Brody, N.P. Burtt, C.P. Cabrera, B.E. Cade, J.F. Chai, X. Chai, L. Chang, C. Chen, B.H. Chen, K.N. Chitrala, Y. Chiu, H.G. de Haan, G.E. Delgado, A. Demirkan, Q. Duan, J. Engmann, S.A. Fatumo, J. Gayán, F. Giulianini, J.H. Gong, S. Gustafsson, Y. Hai, F.P. Hartwig, J. He, Y. Heianza, T. Huang, A. Huerta-Chagoya, M.Y. Hwang, R.A. Jensen, T. Kawaguchi, K.A. Kentistou, Y.J. Kim, M.E. Kleber, I.K. Kooner, S. Lai, L.A. Lange, C.D. Langefeld, M. Lauzon, M. Li, S. Ligthart, J. Liu, M. Loh, J. Long, V. Lyssenko, M. Mangino, C. Marzi, M.E. Montasser, A. Nag, M. Nakatochi, D. Noce, R. Noordam, G. Pistis, M. Preuss, L. Raffield, L.J. Rasmussen-Torvik, S.S. Rich, N.R. Robertson, R. Rueedi, K. Ryan, S. Sanna, R. Saxena, K.E. Schraut, B. Sennblad, K. Setoh, A.V. Smith, T. Sparsø, R.J. Strawbridge, F. Takeuchi, J. Tan, S. Trompet, E. van den Akker, P.J. van der Most, N. Verweij, M. Vogel, H. Wang, C. Wang, N. Wang, H.R. Warren, W. Wen, T. Wilsgaard, A. Wong, A.R. Wood, T. Xie, M.H. Zafarmand, J. Zhao, W. Zhao, N. Amin, Z. Arzumanyan, A. Astrup, S.J.L. Bakker, D. Baldassarre, M. Beekman, R.N. Bergman, A. Bertoni, M. Blüher, L.L. Bonnycastle, S.R. Bornstein, D.W. Bowden, Q. Cai, A. Campbell, H. Campbell, Y.C. Chang, E.J.C. de Geus, A. Dehghan, S. Du, G. Eiriksdottir, A.E. Farmaki, M. Frånberg, C. Fuchsberger, Y. Gao, A.P. Gjesing, A. Goel, S. Han, C.A. Hartman, C. Herder, A.A. Hicks, C. Hsieh, W.A. Hsueh, S. Ichihara, M. Igase, M.A. Ikram, W.C. Johnson, M.E. Jørgensen, P.K. Joshi, R.R. Kalyani, F.R. Kandeel, T. Katsuya, C.C. Khor, W. Kiess, I. Kolcic, T. Kuulasmaa, J. Kuusisto, K. Läll, K. Lam, D.A. Lawlor, N.R. Lee, R.N. Lemaitre, H. Li, S. Lin, J. Lindström, A. Linneberg, J. Liu, C. Lorenzo, T. Matsubara, F. Matsuda, G. Mingrone, S. Mooijaart, S. Moon, T. Nabika, G.N. Nadkarni, J.L. Nadler, M. Nelis, M.J. Neville, J.M. Norris, Y. Ohyagi, A. Peters, P.A. Peyser, O. Polasek, Q. Qi, D. Raven, D.F. Reilly, A. Reiner, F. Rivideneira, K. Roll, I. Rudan, C. Sabanayagam, K. Sandow, N. Sattar, A. Schürmann, J. Shi, H.M. Stringham, K.D. Taylor, T.M. Teslovich, B. Thuesen, P.R.H.J. Timmers, E. Tremoli, M.Y. Tsai, A. Uitterlinden, R.M. van Dam, D. van Heemst, A. van Hylckama Vlieg, J.V. van Vliet-Ostaptchouk, J. Vangipurapu, H. Vestergaard, T. Wang, K. Willems van Dijk, T. Zemunik, G.R. Abecasis, L.S. Adair, C.A. Aguilar-Salinas, M.E. Alarcón-Riquelme, P. An, L. Aviles-Santa, D.M. Becker, L.J. Beilin, S. 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Prokopenko, A. Leong, C. Liu, S.C.J. Parker, K.L. Mohlke, C. Langenberg, E. Wheeler, A.P. Morris, I. Barroso
		
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