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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, ; Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium, ; South Asian Type 2 Diabetes (SAT2D) Consortium, ; Mexican American Type 2 Diabetes (MAT2D) Consortium, ; Type 2 Diabetes Genetic Exploration by Nex-generation sequencing in muylti-Ethnic Samples (T2D-GENES) Consortium, ; Mahajan, A; Go, MJ; Zhang, W; Below, JE; Gaulton, KJ; Ferreira, T; Horikoshi, M; Johnson, AD; Ng, MCY; Prokopenko, I; Saleheen, D; Wang, X; Zeggini, E; Abecasis, GR; Adair, LS; Almgren, P; Atalay, M; Aung, T; Baldassarre, D; Balkau, B; Bao, Y; Barnett, AH; Barroso, I; Basit, A; Been, LF; Beilby, J; Bell, GI; Benediktsson, R; Bergman, RN; Boehm, BO; Boerwinkle, E; Bonnycastle, LL; Burtt, N; Cai, Q; Campbell, H; Carey, J; Cauchi, S; Caulfield, M; Chan, JCN; Chang, L-C; Chang, T-J; Chang, Y-C; Charpentier, G; Chen, C-H; Chen, H; Chen, Y-T; Chia, K-S; Chidambaram, M; Chines, PS; Cho, NH; Cho, YM; Chuang, L-M; Collins, FS; Cornelis, MC; Couper, DJ; Crenshaw, AT; van Dam, RM; Danesh, J; Das, D; de Faire, U; Dedoussis, G; Deloukas, P; Dimas, AS; Dina, C; Doney, AS; Donnelly, PJ; Dorkhan, M; van Duijn, C; Dupuis, J; Edkins, S; Elliott, P; Emilsson, V; Erbel, R; Eriksson, JG; Escobedo, J; Esko, T; Eury, E; Florez, JC; Fontanillas, P; Forouhi, NG; Forsen, T; Fox, C; Fraser, RM; Frayling, TM; Froguel, P; Frossard, P; Gao, Y; Gertow, K; Gieger, C; Gigante, B; Grallert, H; Grant, GB; Grrop, LC; Groves, CJ; Grundberg, E; Guiducci, C; Hamsten, A; Han, B-G; Hara, K; Hassanali, N; Hattersley, AT; Hayward, C; Hedman, AK; Herder, C; Hofman, A; Holmen, OL; Hovingh, K; Hreidarsson, AB; Hu, C; Hu, FB; Hui, J; Humphries, SE; Hunt, SE; Hunter, DJ; Hveem, K; Hydrie, ZI; Ikegami, H; Illig, T; Ingelsson, E; Islam, M; Isomaa, B; Jackson, AU; Jafar, T; James, A; Jia, W; Jöckel, K-H; Jonsson, A; Jowett, JBM; Kadowaki, T; Kang, HM; Kanoni, S; Kao, WHL; Kathiresan, S; Kato, N; Katulanda, P; Keinanen-Kiukaanniemi, KM; Kelly, AM; Khan, H; Khaw, K-T; Khor, C-C; Kim, H-L; Kim, S; Kim, YJ; Kinnunen, L; Klopp, N; Kong, A; Korpi-Hyövälti, E; Kowlessur, S; Kraft, P; Kravic, J; Kristensen, MM; Krithika, S; Kumar, A; Kumate, J; Kuusisto, J; Kwak, SH; Laakso, M; Lagou, V; Lakka, TA; Langenberg, C; Langford, C; Lawrence, R; Leander, K; Lee, J-M; Lee, NR; Li, M; Li, X; Li, Y; Liang, J; Liju, S; Lim, W-Y; Lind, L; Lindgren, CM; Lindholm, E; Liu, C-T; Liu, JJ; Lobbens, S; Long, J; Loos, RJF; Lu, W; Luan, J; Lyssenko, V; Ma, RCW; Maeda, S; Mägi, R; Männisto, S; Matthews, DR; Meigs, JB; Melander, O; Metspalu, A; Meyer, J; Mirza, G; Mihailov, E; Moebus, S; Mohan, V; Mohlke, KL; Morris, AD; Mühleisen, TW; Müller-Nurasyid, M; Musk, B; Nakamura, J; Nakashima, E; Navarro, P; Ng, P-K; Nica, AC; Nilsson, PM; Njølstad, I; Nöthen, MM; Ohnaka, K; Ong, TH; Owen, KR; Palmer, CNA; Pankow, JS; Park, KS; Parkin, M; Pechlivanis, S; Pedersen, NL; Peltonen, L; Perry, JRB; Peters, A; Pinidiyapathirage, JM; Platou, CG; Potter, S; Price, JF; Qi, L; Radha, V; Rallidis, L; Rasheed, A; Rathman, W; Rauramaa, R; Raychaudhuri, S; Rayner, NW; Rees, SD; Rehnberg, E; Ripatti, S; Robertson, N; Roden, M; Rossin, EJ; Rudan, I; Rybin, D; Saaristo, TE; Salomaa, V; Saltevo, J; Samuel, M; Sanghera, DK; Saramies, J; Scott, J; Scott, LJ; Scott, RA; Segrè, AV; Sehmi, J; Sennblad, B; Shah, N; Shah, S; Shera, AS; Shu, XO; Shuldiner, AR; SigurÄ‘sson, G; Sijbrands, E; Silveira, A; Sim, X; Sivapalaratnam, S; Small, KS; So, WY; StanĨáková, A; Stefansson, K; Steinbach, G; Steinthorsdottir, V; Stirrups, K; Strawbridge, RJ; Stringham, HM; Sun, Q; Suo, C; Syvänen, A-C; Takayanagi, R; Takeuchi, F; Tay, WT; Teslovich, TM; Thorand, B; Thorleifsson, G; Thorsteinsdottir, U; Tikkanen, E; Trakalo, J; Tremoli, E; Trip, MD; Tsai, FJ; Tuomi, T; Tuomilehto, J; Uitterlinden, AG; Valladares-Salgado, A; Vedantam, S; Veglia, F; Voight, BF; Wang, C; Wareham, NJ; Wennauer, R; Wickremasinghe, AR; Wilsgaard, T; Wilson, JF; Wiltshire, S; Winckler, W; Wong, TY; Wood, AR; Wu, J-Y; Wu, Y; Yamamoto, K; Yamauchi, T; Yang, M; Yengo, L; Yokota, M; Young, R; Zabaneh, D; Zhang, F; Zhang, R; Zheng, W; Zimmet, PZ; Altshuler, D; Bowden, DW; Cho, YS; Cox, NJ; Cruz, M; Hanis, CL; Kooner, J; Lee, J-Y; Seielstad, M; Teo, YY; Boehnke, M; Parra, EJ; Chambers, JC; Tai, ES; McCarthy, MI; Morris, AP

Published Date

  • March 2014

Published In

Volume / Issue

  • 46 / 3

Start / End Page

  • 234 - 244

PubMed ID

  • 24509480

Pubmed Central ID

  • 24509480

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

International Standard Serial Number (ISSN)

  • 1061-4036

Digital Object Identifier (DOI)

  • 10.1038/ng.2897

Language

  • eng