Abstract

Meta-analyses of genome-wide association studies (GWAS) have identified >240 loci associated with type 2 diabetes (T2D), however most loci have been identified in analyses of European-ancestry individuals. To examine T2D risk in East Asian individuals, we meta-analyzed GWAS data in 77,418 cases and 356,122 controls. In the main analysis, we identified 298 distinct association signals at 178 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 56 loci newly implicated in T2D predisposition. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. New associations include signals in/near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect muscle and adipose differentiation. At another locus, eQTLs at two overlapping T2D signals act through two genes, NKX6-3 and ANK1, in different tissues. Association studies in diverse populations identify additional loci and elucidate disease genes, biology, and pathways.

Details

Title
Identification of type 2 diabetes loci in 433,540 East Asian individuals
Author
Spracklen, Cassandra N; Horikoshi, Momoko; Young Jin Kim; Lin, Kuang; Bragg, Fiona; Moon, Sanghoon; Suzuki, Ken; Tam, Claudia; Tabara, Yasuharu; Soo-Heon Kwak; Takeuchi, Fumihiko; Long, Jirong; Lim, Victor; Jin-Fang, Chai; Chen, Chien-Hsiun; Nakatochi, Masahiro; Yao, Jie; Hyeok Sun Choi; Iyengar, Apoorva K; Perrin, Hannah J; Brotman, Sarah M; Van De Bunt, Martijn; Gloyn, Anna L; Below, Jennifer L; Boehnke, Michael; Bowden, Donald W; Chambers, John C; Mahajan, Anubha; Mccarthy, Mark I; Ng, Maggie Cy; Petty, Lauren E; Zhang, Weihua; Morris, Andrew P; Adair, Linda S; Bian, Zheng; Chan, Juliana; Li-Ching, Chang; Miao-Li, Chee; Chen, Yii-Der Ida; Yuan-Tsong, Chen; Chen, Zhengming; Lee-Ming, Chuang; Du, Shufa; Gordon-Larsen, Penny; Gross, Myron; Guo, Xiuqing; Guo, Yu; Han, Sohee; Annie-Green, Howard; Huang, Wei; Yi-Jen, Hung; Hwang, Mi Yeong; Chii-Min Hwu; Ichihara, Sahoko; Isono, Masato; Hye-Mi Jang; Jiang, Guozhi; Jonas, Jost B; Kamatani, Yoichiro; Katsuya, Tomohiro; Kawaguchi, Takahisa; Khor, Chiea-Chuen; Kohara, Katsuhiko; Lee, Myung-Shik; Lee, Nannette R; Li, Liming; Liu, Jianjun; Luk, Andrea O; Lv, Jun; Okada, Yukinori; Pereira, Mark A; Charumathi Sabanayagam; Shi, Jinxiu; Shin, Dong Mun; So, Wing Yee; Takahashi, Atsushi; Tomlinson, Brian; Tsai, Fuu-Jen; Van Dam, Rob M; Yong-Bing, Xiang; Yamamoto, Ken; Yamauchi, Toshimasa; Yoon, Kyungheon; Yu, Canqing; Jian-Min, Yuan; Zhang, Liang; Zheng, Wei; Igase, Michiya; Yoon Shin Cho; Rotter, Jerome I; Ya-Xing, Wang; Sheu, Wayne Hh; Yokota, Mitsuhiro; Wu, Jer-Yuarn; Ching-Yu, Cheng; Tien-Yin, Wong; Xiao-Ou, Shu; Kato, Norihiro; Park, Kyong-Soo; E-Shyong, Tai; Matsuda, Fumihiko; Koh, Woon-Puay; Cw, Ronald, Ma; Maeda, Shiro; Millwood, Iona Y; Lee, Juyoung; Kadowaki, Takashi; Walters, Robin G; Bong-Jo, Kim; Mohlke, Karen L; Sim, Xueling
University/institution
Cold Spring Harbor Laboratory Press
Section
New Results
Publication year
2019
Publication date
Jun 28, 2019
Publisher
Cold Spring Harbor Laboratory Press
Source type
Working Paper
Language of publication
English
DOI
https://doi.org/10.1101/685172
ProQuest document ID
2248790797
Copyright
© 2019. This article is published under http://creativecommons.org/licenses/by/4.0/ (“the License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.