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Identification of Type 2 Diabetes Loci in 433,540 East Asian Individuals

Citation

Spracklen, Cassandra N.; Horikoshi, Momoko; Kim, Young Jin; Lin, Kuang; Bragg, Fiona; Moon, Sanghoon; Suzuki, Ken; Tam, Claudia H. T.; Tabara, Yasuharu; & Kwak, Soo Heon, et al. (2020). Identification of Type 2 Diabetes Loci in 433,540 East Asian Individuals. Nature, 582, 240-5. PMCID: PMC7292783

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.

URL

https://doi.org/10.1038/s41586-020-2263-3

Reference Type

Journal Article

Journal Title

Nature

Author(s)

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

Year Published

2020

Volume Number

582

Pages

240-5

PMCID

PMC7292783

Reference ID

12724