Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility

A. Mahajan, M. Go, W. Zhang, J.E. Below, K.J. Gaulton, T.C. Ferreira, M. Horikoshi, A.D. Johnson, M. Ng, I. Prokopenko, D. Saleheen, X. Wang, E. Zeggini, G.R. Abecasis, L.S. Adair, P. Almgren, M. Atalay, T. Aung, D. Baldassarre, B.J. BalkauY. Bao, A.H. Barnett, I. Barroso, A. Basit, L. Been, John Beilby, G.I. Bell, R. Benediktsson, R.N. Bergman, B. Oboehm, E.A. Boerwinkle, L.L. Bonnycastle, N.P. Burtt, Q. Cai, H.S. Campbell, J. Carey, S.S. Cauchi, M.J. Caulfield, J.C.N. Chan, L. Chang, T. Chang, Y. Chang, G. Charpentier, C. Chen, H. Chen, Y. Chen, K. Chia, M. Chidambaram, P.S. Chines, N. Cho, Y. Cho, L. Chuang, F.S. Collins, M.C. Cornelis, D.J. Couper, A.T. Crenshaw, R.M. Van Dam, J.N. Danesh, D. Das, U.H. Dé Fairé, G.V.Z. Dedoussis, P. Deloukas, A.S. Dimas, C. Dina, A.S.F. Doney, P.J. Donnelly, M. Dorkhan, C.M. Van Duijn, J.P. Dupuis, S.J. Edkins, P.J.W. Elliott, V. Emilsson, R.M. Erbel, J.G. Eriksson, J. Escobedo, T. Esko, E. Eury, J.C. Florez, P. Fontanillas, N.G. Forouhi, T.J. Forsén, C.S. Fox, R.M. Fraser, T.M. Frayling, P. Froguel, P.M. Frossard, Y. Gao, K. Gertow, C. Gieger, B. Gigante, H. Grallert, G.B. Grant, L.C. Groop, C.J. Groves, E. Grundberg, C. Guiducci, A. Hamsten, B. Han, K. Hara, N. Hassanali, A.T. Hattersley, C. Hayward, A.K. Hedman, C. Herder, A.F. Hofman, O.L. Holmen, K.G. Hovingh, A.B. Hreidarsson, C. Hu, F. Hu, Jennie Hui, S.E. Humphries, S.E. Hunt, D.J. Hunter, K. Hveem, Z.I. Hydrie, H. Ikegami, T. Illig, E. Ingelsson, M. Islam, B. Isomaa, A.U. Jackson, T.H. Jafar, Alan James, W. Jia, K.H. Jöckel, A.M. Jönsson, J.B.M. Jowett, T. Kadowaki, H. Kang, S. Kanoni, W.H.L. Kao, S. Kathiresan, N. Kato, P. Katulanda, S.M. Keinänen-Kiukaanniemi, A.M. Kelly, H. Khan, K.T.T. Khaw, C.C. Khor, H. Kim, S. Kim, Y. Kim, L. Kinnunen, N. Klopp, A. Kong, E.A.L. Korpi-Hyövälti, S. Kowlessur, P.L. Kraft, J. Kravic, M.M. Kristensen, S. Krithika, A.R. Kumar, J. Kumate, J. Kuusisto, S. Kwak, M.P. Laakso, V. Lagou, T.A. Lakka, C. Langenberg, C.F. Langford, Robert Lawrence, K. Leander, J. Lee, N. Lee, M. Li, X. Li, Y. Li, J. Liang, S. Liju, W. Lim, L. Lind, C.M. Lindgren, E. Lindholm, C. Liu, J. Liu, S. Lobbens, J. Long, R.J.F. Loos, W. Lü, J. Luan, V. Lyssenko, R.C. Wma, S. Maeda, R. Mägi, S. Männistö, D.R. Matthews, J.B. Meigs, O. Melander, A.K. Metspalu, J.G. Meyer, G.K. Mirza, E. Mihailov, S. Moebus, V.K. Mohan, K.L. Mohlke, A.D. Morris, T. Wmühleisen, M. Müller-Nurasyid, Arthur Musk, J. Nakamura, E. Nakashima, P. Navarro, P. Ng, A.C. Nica, P.M. Nilsson, I. Njølstad, M.M. Nöthen, K. Ohnaka, T. Ong, K.R. Owen, C.N.A. Palmer, J.S. Pankow, K. Park, M.A. Parkin, S. Pechlivanis, N.L. Pedersen, L.J. Peltonen, J.R.B. Perry, A. Peters, J.M. Pinidiyapathirage, C.G.P. Platou, S.C. Potter, J.F. Price, L. Qi, V. Radha, L.S. Rallidis, A. Rasheed, W.G. Rathmann, R. Rauramaa, S. Raychaudhuri, N.W. Rayner, S.D.R. Rees, E. Rehnberg, S.O. Ripatti, N.R. Robertson, M. Roden, E.J. Rossin, I. Rudan, D.V. Rybin, T.E. Saaristo, V.V. Salomaa, J.T. Saltevo, M. Samuel, D. Ksanghera, J. Saramies, J.M. Scott, L.J. Scott, R.A.H. Scott, A.V. Segrè, J.S. Sehmi, B. Sennblad, N. Shah, S.H. Shah, A.S. Shera, X. Shu, A.R. Shuldiner, G. Sigurǒsson, E.J.G. Sijbrands, A.M.V. Silveira, X. Sim, S. Sivapalaratnam, K.S. Small, W. So, A. Stančáková, K. Stefánsson, G. Steinbach, V. Steinthorsdottir, K. Stirrups, R.J. Strawbridge, H.M. Stringham, Q. Sun, C. Suo, A.C. Syvänen, R. Takayanagi, F. Takeuchi, W. Tay, T.M. Teslovich, B. Thorand, G. Thorleifsson, U. Thorsteinsdóttir, E. Tikkanen, J.M. Trakalo, E. Tremoli, M.D. Trip, F. Tsai, T.M. Tuomi, J.O.I. Tuomilehto, A.G. Uitterlinden, A. Valladares-Salgado, S. Vedantam, F. Veglia, B.F. Voight, C. Wang, N.J. Wareham, R. Wennauer, A.R. Wickremasinghe, T. Wilsgaard, J.F. Wilson, S. Wiltshire, W.M. Winckler, T.Y. Wong, A.R. Wood, J. Wu, Y. Wu, K. Yamamoto, T. Yamauchi, M. Yang, L. Yengo, M. Yokota, R. Young, D. Zabaneh, F. Zhang, R. Zhang, W. Zheng, P.Z. Zimmet, D.M. Altshuler, D.W. Bowden, N.J. Cox, M.T. Cruz, C.L. Hanis, J.S. Kooner, M. Seielstad, Y.Y. Teo, M. Boehnke, E.J. Parra, J.C. Chambers, E.S. Tai, M.I. Mccarthy, A.P. Morris

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Abstract

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry. © 2014 Nature America, Inc. © 2014 Nature America, Inc.
Original languageEnglish
Pages (from-to)234-244
JournalNature Genetics
Volume46
Issue number3
DOIs
Publication statusPublished - 2014

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Mahajan, A., Go, M., Zhang, W., Below, J. E., Gaulton, K. J., Ferreira, T. C., ... Morris, A. P. (2014). Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. Nature Genetics, 46(3), 234-244. https://doi.org/10.1038/ng.2897