Identification of type 2 diabetes loci in 433,540 East Asian individuals

Cassandra N. Spracklen, Momoko Horikoshi, Young Jin Kim, Kuang Lin, Fiona Bragg, Sanghoon Moon, Ken Suzuki, Claudia H.T. Tam, Yasuharu Tabara, Soo Heon Kwak, Fumihiko Takeuchi, Jirong Long, Victor J.Y. Lim, Jin Fang Chai, Chien Hsiun Chen, Masahiro Nakatochi, Jie Yao, Hyeok Sun Choi, Apoorva K. Iyengar, Hannah J. PerrinSarah M. Brotman, Martijn van de Bunt, Anna L. Gloyn, Jennifer E. Below, Michael Boehnke, Donald W. Bowden, John C. Chambers, Anubha Mahajan, Mark I. McCarthy, Maggie C.Y. Ng, Lauren E. Petty, Weihua Zhang, Andrew P. Morris, Linda S. Adair, Masato Akiyama, Zheng Bian, Juliana C.N. Chan, Li Ching Chang, Miao Li Chee, Yii Der Ida Chen, Yuan Tsong Chen, Zhengming Chen, Lee Ming Chuang, Shufa Du, Penny Gordon-Larsen, Myron Gross, Xiuqing Guo, Yu Guo, Sohee Han, Annie Green Howard, Wei Huang, Yi Jen Hung, Mi Yeong Hwang, Chii Min Hwu, Sahoko Ichihara, Masato Isono, Hye Mi Jang, Guozhi Jiang, Jost B. Jonas, Yoichiro Kamatani, Tomohiro Katsuya, Takahisa Kawaguchi, Chiea Chuen Khor, Katsuhiko Kohara, Myung Shik Lee, Nanette R. Lee, Liming Li, Jianjun Liu, Andrea O. Luk, Jun Lv, Yukinori Okada, Mark A. Pereira, Charumathi Sabanayagam, Jinxiu Shi, Dong Mun Shin, Wing Yee So, Atsushi Takahashi, Brian Tomlinson, Fuu Jen Tsai, Rob M. van Dam, Yong Bing Xiang, Ken Yamamoto, Toshimasa Yamauchi, Kyungheon Yoon, Canqing Yu, Jian Min Yuan, Liang Zhang, Wei Zheng, Michiya Igase, Yoon Shin Cho, Jerome I. Rotter, Ya Xing Wang, Wayne H.H. Sheu, Mitsuhiro Yokota, Jer Yuarn Wu, Ching Yu Cheng, Tien Yin Wong, Xiao Ou Shu, Norihiro Kato, Kyong Soo Park, E. Shyong Tai, Fumihiko Matsuda, Woon Puay Koh, Ronald C.W. Ma, Shiro Maeda, Iona Y. Millwood, Juyoung Lee, Takashi Kadowaki, Robin G. Walters, Bong Jo Kim, Karen L. Mohlke, Xueling Sim

Research output: Contribution to journalArticle

Abstract

Meta-analyses of genome-wide association studies (GWAS) have identified more than 240 loci that are associated with type 2 diabetes (T2D)1,2; however, most of these loci have been identified in analyses of individuals with European ancestry. Here, to examine T2D risk in East Asian individuals, we carried out a meta-analysis of GWAS data from 77,418 individuals with T2D and 356,122 healthy control individuals. In the main analysis, we identified 301 distinct association signals at 183 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 61 loci that are newly implicated in predisposition to T2D. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. Previously undescribed associations include signals in or near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect the differentiation of muscle and adipose cells3. At another locus, expression quantitative trait loci at two overlapping T2D signals affect two genes—NKX6-3 and ANK1—in different tissues4–6. Association studies in diverse populations identify additional loci and elucidate disease-associated genes, biology, and pathways.

Original languageEnglish
Pages (from-to)240-245
Number of pages6
JournalNature
Volume582
Issue number7811
DOIs
Publication statusPublished - Jun 11 2020

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    Spracklen, C. N., Horikoshi, M., Kim, Y. J., Lin, K., Bragg, F., Moon, S., Suzuki, K., Tam, C. H. T., Tabara, Y., Kwak, S. H., Takeuchi, F., Long, J., Lim, V. J. Y., Chai, J. F., Chen, C. H., Nakatochi, M., Yao, J., Choi, H. S., Iyengar, A. K., ... Sim, X. (2020). Identification of type 2 diabetes loci in 433,540 East Asian individuals. Nature, 582(7811), 240-245. https://doi.org/10.1038/s41586-020-2263-3