| Title | Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation. |
| Publication Type | Journal Article |
| Year of Publication | 2022 |
| Authors | Mahajan, A, Spracklen, CN, Zhang, W, C Y Ng, M, Petty, LE, Kitajima, H, Yu, GZ, Rüeger, S, Speidel, L, Kim, YJin, Horikoshi, M, Mercader, JM, Taliun, D, Moon, S, Kwak, S-H, Robertson, NR, Rayner, NW, Loh, M, Kim, B-J, Chiou, J, Miguel-Escalada, I, Parolo, PDella Brio, Lin, K, Bragg, F, Preuss, MH, Takeuchi, F, Nano, J, Guo, X, Lamri, A, Nakatochi, M, Scott, RA, Lee, J-J, Huerta-Chagoya, A, Graff, M, Chai, J-F, Parra, EJ, Yao, J, Bielak, LF, Tabara, Y, Hai, Y, Steinthorsdottir, V, Cook, JP, Kals, M, Grarup, N, Schmidt, EM, Pan, I, Sofer, T, Wuttke, M, Sarnowski, C, Gieger, C, Nousome, D, Trompet, S, Long, J, Sun, M, Tong, L, Chen, W-M, Ahmad, M, Noordam, R, J Y Lim, V, Tam, CHT, Joo, YYoonie, Chen, C-H, Raffield, LM, Lecoeur, C, Prins, BPeter, Nicolas, A, Yanek, LR, Chen, G, Jensen, RA, Tajuddin, S, Kabagambe, EK, An, P, Xiang, AH, Choi, HSun, Cade, BE, Tan, J, Flanagan, J, Abaitua, F, Adair, LS, Adeyemo, A, Aguilar-Salinas, CA, Akiyama, M, Anand, SS, Bertoni, A, Bian, Z, Bork-Jensen, J, Brandslund, I, Brody, JA, Brummett, CM, Buchanan, TA, Canouil, M, Chan, JCN, Chang, L-C, Chee, M-L, Chen, J, Chen, S-H, Chen, Y-T, Chen, Z, Chuang, L-M, Cushman, M, Das, SK, H de Silva, J, Dedoussis, G, Dimitrov, L, Doumatey, AP, Du, S, Duan, Q, Eckardt, K-U, Emery, LS, Evans, DS, Evans, MK, Fischer, K, Floyd, JS, Ford, I, Fornage, M, Franco, OH, Frayling, TM, Freedman, BI, Fuchsberger, C, Genter, P, Gerstein, HC, Giedraitis, V, González-Villalpando, C, Gonzalez-Villalpando, MElena, Goodarzi, MO, Gordon-Larsen, P, Gorkin, D, Gross, M, Guo, Y, Hackinger, S, Han, S, Hattersley, AT, Herder, C, Howard, A-G, Hsueh, W, Huang, M, Huang, W, Hung, Y-J, Hwang, MYeong, Hwu, C-M, Ichihara, S, Ikram, MArfan, Ingelsson, M, Islam, MTariqul, Isono, M, Jang, H-M, Jasmine, F, Jiang, G, Jonas, JB, Jørgensen, ME, Jørgensen, T, Kamatani, Y, Kandeel, FR, Kasturiratne, A, Katsuya, T, Kaur, V, Kawaguchi, T, Keaton, JM, Kho, AN, Khor, C-C, Kibriya, MG, Kim, D-H, Kohara, K, Kriebel, J, Kronenberg, F, Kuusisto, J, Läll, K, Lange, LA, Lee, M-S, Lee, NR, Leong, A, Li, L, Li, Y, Li-Gao, R, Ligthart, S, Lindgren, CM, Linneberg, A, Liu, C-T, Liu, J, Locke, AE, Louie, T, Luan, J'an, Luk, AO, Luo, X, Lv, J, Lyssenko, V, Mamakou, V, Mani, RK, Meitinger, T, Metspalu, A, Morris, AD, Nadkarni, GN, Nadler, JL, Nalls, MA, Nayak, U, Nongmaithem, SS, Ntalla, I, Okada, Y, Orozco, L, Patel, SR, Pereira, MA, Peters, A, Pirie, FJ, Porneala, B, Prasad, G, Preissl, S, Rasmussen-Torvik, LJ, Reiner, AP, Roden, M, Rohde, R, Roll, K, Sabanayagam, C, Sander, M, Sandow, K, Sattar, N, Schönherr, S, Schurmann, C, Shahriar, M, Shi, J, Shin, DMun, Shriner, D, Smith, JA, So, WYee, Stančáková, A, Stilp, AM, Strauch, K, Suzuki, K, Takahashi, A, Taylor, KD, Thorand, B, Thorleifsson, G, Thorsteinsdottir, U, Tomlinson, B, Torres, JM, Tsai, F-J, Tuomilehto, J, Tusié-Luna, T, Udler, MS, Valladares-Salgado, A, van Dam, RM, van Klinken, JB, Varma, R, Vujkovic, M, Wacher-Rodarte, N, Wheeler, E, Whitsel, EA, Wickremasinghe, AR, van Dijk, KW, Witte, DR, Yajnik, CS, Yamamoto, K, Yamauchi, T, Yengo, L, Yoon, K, Yu, C, Yuan, J-M, Yusuf, S, Zhang, L, Zheng, W, Raffel, LJ, Igase, M, Ipp, E, Redline, S, Cho, YS, Lind, L, Province, MA, Hanis, CL, Peyser, PA, Ingelsson, E, Zonderman, AB, Psaty, BM, Wang, Y-X, Rotimi, CN, Becker, DM, Matsuda, F, Liu, Y, Zeggini, E, Yokota, M, Rich, SS, Kooperberg, C, Pankow, JS, Engert, JC, Chen, Y-DI, Froguel, P, Wilson, JG, Sheu, WHH, Kardia, SLR, Wu, J-Y, M Hayes, G, Ma, RCW, Wong, T-Y, Groop, L, Mook-Kanamori, DO, Chandak, GR, Collins, FS, Bharadwaj, D, Paré, G, Sale, MM, Ahsan, H, Motala, AA, Shu, X-O, Park, K-S, J Jukema, W, Cruz, M, McKean-Cowdin, R, Grallert, H, Cheng, C-Y, Bottinger, EP, Dehghan, A, Tai, E-S, Dupuis, J, Kato, N, Laakso, M, Köttgen, A, Koh, W-P, Palmer, CNA, Liu, S, Abecasis, G, Kooner, JS, Loos, RJF, North, KE, Haiman, CA, Florez, JC, Saleheen, D, Hansen, T, Pedersen, O, Mägi, R, Langenberg, C, Wareham, NJ, Maeda, S, Kadowaki, T, Lee, J, Millwood, IY, Walters, RG, Stefansson, K, Myers, SR, Ferrer, J, Gaulton, KJ, Meigs, JB, Mohlke, KL, Gloyn, AL, Bowden, DW, Below, JE, Chambers, JC, Sim, X, Boehnke, M, Rotter, JI, McCarthy, MI, Morris, AP |
| Corporate/Institutional Authors | FinnGen, eMERGE Consortium |
| Journal | Nat Genet |
| Volume | 54 |
| Issue | 5 |
| Pagination | 560-572 |
| Date Published | 2022 May |
| ISSN | 1546-1718 |
| Keywords | Diabetes Mellitus, Type 2, Ethnicity, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Risk Factors |
| Abstract | <p>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), 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.</p> |
| DOI | 10.1038/s41588-022-01058-3 |
| Alternate Journal | Nat Genet |
| PubMed ID | 35551307 |
| PubMed Central ID | PMC9179018 |
| Grant List | R01 DK098032 / DK / NIDDK NIH HHS / United States
R01 HL142302 / HL / NHLBI NIH HHS / United States
U01 DK085545 / DK / NIDDK NIH HHS / United States
U01 DK105535 / DK / NIDDK NIH HHS / United States |
