DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Consortium AGENTD (AGEN T, Consortium SATD (SAT2D), Consortium MATD (MAT2D), Consortium TDGEN generation S (T2D G, Mahajan A, Go MJ, Zhang W, Below J, Gaulton K, Ferreira T, Horikoshi M, Johnson A, Ng M, Prokopenko I, Saleheen D, Wang X, Zeggini E, Abecasis G, Adair L, Almgren P, Atalay M, Aung T, Baldassarre D, Balkau B, Bao Y, Barnett A, Barroso I, Basit A, Been L, Beilby J, Bell G, Benediktsson R, Bergman R, Boehm B, Boerwinkle E, Bonnycastle L, Burtt N, Cai Q, Campbell H, Carey J, Cauchi S, Caulfield M, Chan J, Chang LC, Chang TJ, Chang YC, Charpentier G, Chen CH, Chen H, Chen YT, Chia KS, Chidambaram M, Chines P, Cho N, Cho YM, Chuang LM, Collins F, Cornelis M, Couper D, Crenshaw A, Dam R, Danesh J, Das D, Faire U, Dedoussis G, Deloukas P, Dimas A, Dina C, Doney A, Donnelly P, Dorkhan M, Duijn C, Dupuis J, Edkins S, Elliott P, Emilsson V, Erbel R, Eriksson J, Escobedo J, Esko T, Eury E, Florez J, Fontanillas P, Forouhi N, Forsen T, Fox C, Fraser R, Frayling T, Froguel P, Frossard P, Gao Y, Gertow K, Gieger C, Gigante B, Grallert H, Grant G, Grrop L, Groves C, Grundberg E, Guiducci C, Hamsten A, Han BG, Hara K, Hassanali N, Hattersley A, Hayward C, Hedman A, Herder C, Hofman A, Holmen O, Hovingh K, Hreidarsson A, Hu C, Hu F, Hui J, Humphries S, Hunt S, Hunter D, Hveem K, Hydrie Z, Ikegami H, Illig T, Ingelsson E, Islam M, Isomaa B, Jackson A, Jafar T, James A, Jia W, Jöckel KH, Jonsson A, Jowett J, Kadowaki T, Kang HM, Kanoni S, Kao WH, Kathiresan S, Kato N, Katulanda P, Keinanen-Kiukaanniemi K, Kelly A, Khan H, Khaw KT, Khor CC, Kim HL, Kim S, Kim YJ, Kinnunen L, Klopp N, Kong A, Korpi-Hyövälti E, Kowlessur S, Kraft P, Kravic J, Kristensen M, Krithika, Kumar A, Kumate J, Kuusisto J, Kwak SH, Laakso M, Lagou V, Lakka T, Langenberg C, Langford C, Lawrence R, Leander K, Lee JM, Lee N, Li M, Li X, Li Y, Liang J, Liju S, Lim WY, Lind L, Lindgren C, Lindholm E, Liu CT, Liu J, Lobbens S, Long J, Loos R, Lu W, Luan J, Lyssenko V, Ma R, Maeda S, Mägi R, Männistö S, Matthews D, Meigs J, Melander O, Metspalu A, Meyer J, Mirza G, Mihailov E, Moebus S, Mohan V, Mohlke K, Morris A, Mühleisen T, Müller-Nurasyid M, Musk B, Nakamura J, Nakashima E, Navarro P, Ng PK, Nica A, Nilsson P, Njølstad I, Nöthen M, Ohnaka K, Ong TH, Owen K, Palmer C, Pankow J, Park KS, Parkin M, Pechlivanis S, Pedersen N, Peltonen L, Perry J, Peters A, Pinidiyapathirage J, Platou C, Potter S, Price J, Qi L, Radha V, Rallidis L, Rasheed A, Rathman W, Rauramaa R, Raychaudhuri S, Rayner W, Rees S, Rehnberg E, Ripatti S, Robertson N, Roden M, Rossin E, Rudan I, Rybin D, Saaristo T, Salomaa V, Saltevo J, Samuel M, Sanghera D, Saramies J, Scott J, Scott L, Scott R, Segrè A, Sehmi J, Sennblad B, Shah N, Shah S, Shera S, Ou Shu X, Shuldiner A, Sigurđsson G, Sijbrands E, Silveira A, Sim X, Sivapalaratnam S, Small K, So WY, Stančáková A, Stefansson K, Steinbach G, Steinthorsdottir V, Stirrups K, Strawbridge R, Stringham H, Sun Q, Suo C, Syvänen AC, Takayanagi R, Takeuchi F, Tay WT, Teslovich T, Thorand B, Thorleifsson G, Thorsteinsdottir U, Tikkanen E, Trakalo J, Tremoli E, Trip M, Tsai FJ, Tuomi T, Tuomilehto J, Uitterlinden A, Valladares-Salgado A, Vedantam S, Veglia F, Voight B, Wang C, Wareham N, Wennauer R, Wickremasinghe A, Wilsgaard T, Wilson J, Wiltshire S, Winckler W, Wong TY, Wood A, Wu JY, Wu Y, Yamamoto K, Yamauchi T, Yang M, Yengo L, Yokota M, Young R, Zabaneh D, Zhang F, Zhang R, Zheng W, Zimmet P, Altshuler D, Bowden D, Cho YS, Cox N, Cruz M, Hanis C, Kooner J, Lee JY, Seielstad M, Teo YY, Boehnke M, Parra E, Chambers J, Tai S, McCarthy M, Morris A. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. Nat Genet. 2014;46(3):234–44.
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.
Last updated on 03/06/2023