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, A 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

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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 cells 3. At another locus, expression quantitative trait loci at two overlapping T2D signals affect two genes—NKX6-3 and ANK1—in different tissues 4–6. 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
Early online date6 May 2020
DOIs
Publication statusPublished - 11 Jun 2020

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