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| Item Type: | Article |
|---|---|
| Title: | Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation |
| Creators Name: | Mahajan, A. and Spracklen, C.N. and Zhang, W. and Ng, M.C.Y. and Petty, L.E. and Kitajima, H. and Yu, G.Z. and Rüeger, S. and Speidel, L. and Kim, Y.J. and Horikoshi, M. and Mercader, J.M. and Taliun, D. and Moon, S. and Kwak, S.H. and Robertson, N.R. and Rayner, N.W. and Loh, M. and Kim, B.J. and Chiou, J. and Miguel-Escalada, I. and Della Briotta Parolo, P. and Lin, K. and Bragg, F. and Preuss, M.H. and Takeuchi, F. and Nano, J. and Guo, X. and Lamri, A. and Nakatochi, M. and Scott, R.A. and Lee, J.. and Huerta-Chagoya, A. and Graff, M. and Chai, J.F. and Parra, E.J. and Yao, J. and Bielak, L.F. and Tabara, Y. and Hai, Y. and Steinthorsdottir, V. and Cook, J.P. and Kals, M. and Grarup, N. and Schmidt, E.M. and Pan, I. and Sofer, T. and Wuttke, M. and Sarnowski, C. and Gieger, C. and Nousome, D. and Trompet, S. and Long, J. and Sun, M. and Tong, L. and Chen, W.M. and Ahmad, M. and Noordam, R. and Lim, V.J.Y. and Tam, C.H.T. and Joo, Y.Y. and Chen, C.H. and Raffield, L.M. and Lecoeur, C. and Prins, B.P. and Nicolas, A. and Yanek, L.R. and Chen, G. and Jensen, R.A. and Tajuddin, S. and Kabagambe, E.K. and An, P. and Xiang, A.H. and Choi, H.S. and Cade, B.E. and Tan, J. and Flanagan, J. and Abaitua, F. and Adair, L.S. and Adeyemo, A. and Aguilar-Salinas, C.A. and Akiyama, M. and Anand, S.S. and Bertoni, A. and Bian, Z. and Bork-Jensen, J. and Brandslund, I. and Brody, J.A. and Brummett, C.M. and Buchanan, T.A. and Canouil, M. and Chan, J.C.N. and Chang, L.C. and Chee, M.L. and Chen, J. and Chen, S.H. and Chen, Y.T. and Chen, Z. and Chuang, L.M. and Cushman, M. and Das, S.K. and de Silva, H.J. and Dedoussis, G. and Dimitrov, L. and Doumatey, A.P. and Du, S. and Duan, Q. and Eckardt, K.U. and Emery, L.S. and Evans, D.S. and Evans, M.K. and Fischer, K. and Floyd, J.S. and Ford, I. and Fornage, M. and Franco, O.H. and Frayling, T.M. and Freedman, B.I. and Fuchsberger, C. and Genter, P. and Gerstein, H.C. and Giedraitis, V. and González-Villalpando, C. and González-Villalpando, M.E. and Goodarzi, M.O. and Gordon-Larsen, P. and Gorkin, D. and Gross, M. and Guo, Y. and Hackinger, S. and Han, S. and Hattersley, A.T. and Herder, C. and Howard, A.G. and Hsueh, W. and Huang, M. and Huang, W. and Hung, Y.J. and Hwang, M.Y. and Hwu, C.M. and Ichihara, S. and Ikram, M.A. and Ingelsson, M. and Islam, M.T. and Isono, M. and Jang, H.M. and Jasmine, F. and Jiang, G. and Jonas, J.B. and Jørgensen, M.E. and Jørgensen, T. and Kamatani, Y. and Kandeel, F.R. and Kasturiratne, A. and Katsuya, T. and Kaur, V. and Kawaguchi, T. and Keaton, J.M. and Kho, A.N. and Khor, C.C. and Kibriya, M.G. and Kim, D.H. and Kohara, K. and Kriebel, J. and Kronenberg, F. and Kuusisto, J. and Läll, K. and Lange, L.A. and Lee, M.S. and Lee, N.R. and Leong, A. and Li, L. and Li, Y. and Li-Gao, R. and Ligthart, S. and Lindgren, C.M. and Linneberg, A. and Liu, C.T. and Liu, J. and Locke, A.E. and Louie, T. and Luan, J. and Luk, A.O. and Luo, X. and Lv, J. and Lyssenko, V. and Mamakou, V. and Mani, K.R. and Meitinger, T. and Metspalu, A. and Morris, A.D. and Nadkarni, G.N. and Nadler, J.L. and Nalls, M.A. and Nayak, U. and Nongmaithem, S.S. and Ntalla, I. and Okada, Y. and Orozco, L. and Patel, S.R. and Pereira, M.A. and Peters, A. and Pirie, F.J. and Porneala, B. and Prasad, G. and Preissl, S. and Rasmussen-Torvik, L.J. and Reiner, A.P. and Roden, M. and Rohde, R. and Roll, K. and Sabanayagam, C. and Sander, M. and Sandow, K. and Sattar, N. and Schönherr, S. and Schurmann, C. and Shahriar, M. and Shi, J. and Shin, D.M. and Shriner, D. and Smith, J.A. and So, W.Y. and Stančáková, A. and Stilp, A.M. and Strauch, K. and Suzuki, K. and Takahashi, A. and Taylor, K.D. and Thorand, B. and Thorleifsson, G. and Thorsteinsdottir, U. and Tomlinson, B. and Torres, J.M. and Tsai, F.J. and Tuomilehto, J. and Tusie-Luna, T. and Udler, M.S. and Valladares-Salgado, A. and van Dam, R.M. and van Klinken, J.B. and Varma, R. and Vujkovic, M. and Wacher-Rodarte, N. and Wheeler, E. and Whitsel, E.A. and Wickremasinghe, A.R. and van Dijk, K.W. and Witte, D.R. and Yajnik, C.S. and Yamamoto, K. and Yamauchi, T. and Yengo, L. and Yoon, K. and Yu, C. and Yuan, J.M. and Yusuf, S. and Zhang, L. and Zheng, W. and Raffel, L.J. and Igase, M. and Ipp, E. and Redline, S. and Cho, Y.S. and Lind, L. and Province, M.A. and Hanis, C.L. and Peyser, P.A. and Ingelsson, E. and Zonderman, A.B. and Psaty, B.M. and Wang, Y.X. and Rotimi, C.N. and Becker, D.M. and Matsuda, F. and Liu, Y. and Zeggini, E. and Yokota, M. and Rich, S.S. and Kooperberg, C. and Pankow, J.S. and Engert, J.C. and Chen, Y.D.I. and Froguel, P. and Wilson, J.G. and Sheu, W.H.H. and Kardia, S.L.R. and Wu, J.Y. and Hayes, M.G. and Ma, R.C.W. and Wong, T.Y. and Groop, L. and Mook-Kanamori, D.O. and Chandak, G.R. and Collins, F.S. and Bharadwaj, D. and Paré, G. and Sale, M.M. and Ahsan, H. and Motala, A.A. and Shu, X.O. and Park, K.S. and Jukema, J.W. and Cruz, M. and McKean-Cowdin, R. and Grallert, H. and Cheng, C.Y. and Bottinger, E.P. and Dehghan, A. and Tai, E.S. and Dupuis, J. and Kato, N. and Laakso, M. and Köttgen, A. and Koh, W.P. and Palmer, C.N A. and Liu, S. and Abecasis, G. and Kooner, J.S. and Loos, R.J.F. and North, K.E. and Haiman, C.A. and Florez, J.C. and Saleheen, D. and Hansen, T. and Pedersen, O. and Mägi, R. and Langenberg, C. and Wareham, N.J. and Maeda, S. and Kadowaki, T. and Lee, J. and Millwood, I.Y. and Walters, R.G. and Stefansson, K. and Myers, S.R. and Ferrer, J. and Gaulton, K.J. and Meigs, J.B. and Mohlke, K.L. and Gloyn, A.L. and Bowden, D.W. and Below, J.E. and Chambers, J.C. and Sim, X. and Boehnke, M. and Rotter, J.I. and McCarthy, M.I. and Morris, A.P. |
| Abstract: | We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 × 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. |
| Keywords: | Ethnicity, Genetic Predisposition to Disease, Genome-Wide Association Study, Risk Factors, Single Nucleotide Polymorphism, Type 2 Diabetes Mellitus |
| Source: | Nature Genetics |
| ISSN: | 1061-4036 |
| Publisher: | Nature Publishing Group |
| Volume: | 54 |
| Number: | 5 |
| Page Range: | 560-572 |
| Date: | May 2022 |
| Official Publication: | https://doi.org/10.1038/s41588-022-01058-3 |
| PubMed: | View item in PubMed |
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