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

  • Author(s): Spracklen, Cassandra N
  • Horikoshi, Momoko
  • Kim, Young Jin
  • Lin, Kuang
  • Bragg, Fiona
  • Moon, Sanghoon
  • Suzuki, Ken
  • Tam, Claudia HT
  • Tabara, Yasuharu
  • Kwak, Soo-Heon
  • Takeuchi, Fumihiko
  • Long, Jirong
  • Lim, Victor JY
  • 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 CY
  • Petty, Lauren E
  • Zhang, Weihua
  • Morris, Andrew P
  • Adair, Linda S
  • Akiyama, Masato
  • Bian, Zheng
  • Chan, Juliana CN
  • 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
  • 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 HH
  • 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 CW
  • Maeda, Shiro
  • Millwood, Iona Y
  • Lee, Juyoung
  • Kadowaki, Takashi
  • Walters, Robin G
  • Kim, Bong-Jo
  • Mohlke, Karen L
  • Sim, Xueling
  • et al.
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.

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