Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation

Mahajan, A. et al. (2022) Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation. Nature Genetics, 54(5), pp. 560-572. (doi: 10.1038/s41588-022-01058-3) (PMID:35551307)

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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), 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Sattar, Professor Naveed and Ford, Professor Ian
Authors: Mahajan, A., Spracklen, C. N., Zhang, W., Ng, M. C. Y., Petty, L. E., Kitajima, H., Yu, G. Z., Rüeger, S., Speidel, L., Kim, Y. J., Horikoshi, M., Mercader, J. M., Taliun, D., Moon, S., Kwak, S.-H., Robertson, N. R., Rayner, N. W., Loh, M., Kim, B.-J., Chiou, J., Miguel-Escalada, I., Della Briotta Parolo, P., Lin, K., Bragg, F., Preuss, M. H., Takeuchi, F., Nano, J., Guo, X., Lamri, A., Nakatochi, M., Scott, R. A., Lee, J.-J., Huerta-Chagoya, A., Graff, M., Chai, J.-F., Parra, E. J., Yao, J., Bielak, L. F., Tabara, Y., Hai, Y., Steinthorsdottir, V., Cook, J. P., Kals, M., Grarup, N., Schmidt, E. M., 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., Lim, V. J. Y., Tam, C. H. T., Joo, Y. Y., Chen, C.-H., Raffield, L. M., Lecoeur, C., Prins, B. P., Nicolas, A., Yanek, L. R., Chen, G., Jensen, R. A., Tajuddin, S., Kabagambe, E. K., An, P., Xiang, A. H., Choi, H. S., Cade, B. E., Tan, J., Flanagan, J., Abaitua, F., Adair, L. S., Adeyemo, A., Aguilar-Salinas, C. A., Akiyama, M., Anand, S. S., Bertoni, A., Bian, Z., Bork-Jensen, J., Brandslund, I., Brody, J. A., Brummett, C. M., Buchanan, T. A., Canouil, M., Chan, J. C. N., Chang, L.-C., Chee, M.-L., Chen, J., Chen, S.-H., Chen, Y.-T., Chen, Z., Chuang, L.-M., Cushman, M., Das, S. K., de Silva, H. J., Dedoussis, G., Dimitrov, L., Doumatey, A. P., Du, S., Duan, Q., Eckardt, K.-U., Emery, L. S., Evans, D. S., Evans, M. K., Fischer, K., Floyd, J. S., Ford, I., Fornage, M., Franco, O. H., Frayling, T. M., Freedman, B. I., Fuchsberger, C., Genter, P., Gerstein, H. C., Giedraitis, V., González-Villalpando, C., González-Villalpando, M. E., Goodarzi, M. O., Gordon-Larsen, P., Gorkin, D., Gross, M., Guo, Y., Hackinger, S., Han, S., Hattersley, A. T., Herder, C., Howard, A.-G., Hsueh, W., Huang, M., Huang, W., Hung, Y.-J., Hwang, M. Y., Hwu, C.-M., Ichihara, S., Ikram, M. A., Ingelsson, M., Islam, M. T., Isono, M., Jang, H.-M., Jasmine, F., Jiang, G., Jonas, J. B., Jørgensen, M. E., Jørgensen, T., Kamatani, Y., Kandeel, F. R., Kasturiratne, A., Katsuya, T., Kaur, V., Kawaguchi, T., Keaton, J. M., Kho, A. N., Khor, C.-C., Kibriya, M. G., Kim, D.-H., Kohara, K., Kriebel, J., Kronenberg, F., Kuusisto, J., Läll, K., Lange, L. A., Lee, M.-S., Lee, N. R., Leong, A., Li, L., Li, Y., Li-Gao, R., Ligthart, S., Lindgren, C. M., Linneberg, A., Liu, C.-T., Liu, J., Locke, A. E., Louie, T., Luan, J.'a., Luk, A. O., Luo, X., Lv, J., Lyssenko, V., Mamakou, V., Mani, K. R., Meitinger, T., Metspalu, A., Morris, A. D., Nadkarni, G. N., Nadler, J. L., Nalls, M. A., Nayak, U., Nongmaithem, S. S., Ntalla, I., Okada, Y., Orozco, L., Patel, S. R., Pereira, M. A., Peters, A., Pirie, F. J., Porneala, B., Prasad, G., Preissl, S., Rasmussen-Torvik, L. J., Reiner, A. P., Roden, M., Rohde, R., Roll, K., Sabanayagam, C., Sander, M., Sandow, K., Sattar, N., Schönherr, S., Schurmann, C., Shahriar, M., Shi, J., Shin, D. M., Shriner, D., Smith, J. A., So, W. Y., Stančáková, A., Stilp, A. M., Strauch, K., Suzuki, K., Takahashi, A., Taylor, K. D., Thorand, B., Thorleifsson, G., Thorsteinsdottir, U., Tomlinson, B., Torres, J. M., Tsai, F.-J., Tuomilehto, J., Tusie-Luna, T., Udler, M. S., Valladares-Salgado, A., van Dam, R. M., van Klinken, J. B., Varma, R., Vujkovic, M., Wacher-Rodarte, N., Wheeler, E., Whitsel, E. A., Wickremasinghe, A. R., van Dijk, K. W., Witte, D. R., Yajnik, C. S., Yamamoto, K., Yamauchi, T., Yengo, L., Yoon, K., Yu, C., Yuan, J.-M., Yusuf, S., Zhang, L., Zheng, W., Raffel, L. J., Igase, M., Ipp, E., Redline, S., Cho, Y. S., Lind, L., Province, M. A., Hanis, C. L., Peyser, P. A., Ingelsson, E., Zonderman, A. B., Psaty, B. M., Wang, Y.-X., Rotimi, C. N., Becker, D. M., Matsuda, F., Liu, Y., Zeggini, E., Yokota, M., Rich, S. S., Kooperberg, C., Pankow, J. S., Engert, J. C., Chen, Y.-D. I., Froguel, P., Wilson, J. G., Sheu, W. H. H., Kardia, S. L. R., Wu, J.-Y., Hayes, M. G., Ma, R. C. W., Wong, T.-Y., Groop, L., Mook-Kanamori, D. O., Chandak, G. R., Collins, F. S., Bharadwaj, D., Paré, G., Sale, M. M., Ahsan, H., Motala, A. A., Shu, X.-O., Park, K.-S., Jukema, J. W., Cruz, M., McKean-Cowdin, R., Grallert, H., Cheng, C.-Y., Bottinger, E. P., Dehghan, A., Tai, E.-S., Dupuis, J., Kato, N., Laakso, M., Köttgen, A., Koh, W.-P., Palmer, C. N. A., Liu, S., Abecasis, G., Kooner, J. S., Loos, R. J. F., North, K. E., Haiman, C. A., Florez, J. C., Saleheen, D., Hansen, T., Pedersen, O., Mägi, R., Langenberg, C., Wareham, N. J., Maeda, S., Kadowaki, T., Lee, J., Millwood, I. Y., Walters, R. G., Stefansson, K., Myers, S. R., Ferrer, J., Gaulton, K. J., Meigs, J. B., Mohlke, K. L., Gloyn, A. L., Bowden, D. W., Below, J. E., Chambers, J. C., Sim, X., Boehnke, M., Rotter, J. I., McCarthy, M. I., and Morris, A. P.
Subjects:R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
Journal Name:Nature Genetics
Publisher:Nature Research
ISSN:1061-4036
ISSN (Online):1546-1718
Published Online:12 May 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Nature Genetics 54(5): 560-572
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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