Identification of type 2 diabetes loci in 433,540 East Asian individuals.
Spracklen CN., Horikoshi M., Kim YJ., Lin K., Bragg F., Moon S., Suzuki K., Tam CHT., Tabara Y., Kwak S-H., Takeuchi F., Long J., Lim VJY., Chai J-F., Chen C-H., Nakatochi M., Yao J., Choi HS., Iyengar AK., Perrin HJ., Brotman SM., van de Bunt M., Gloyn AL., Below JE., Boehnke M., Bowden DW., Chambers JC., Mahajan A., McCarthy MI., Ng MCY., Petty LE., Zhang W., Morris AP., Adair LS., Akiyama M., Bian Z., Chan JCN., Chang L-C., Chee M-L., Chen Y-DI., Chen Y-T., Chen Z., Chuang L-M., Du S., Gordon-Larsen P., Gross M., Guo X., Guo Y., Han S., Howard A-G., Huang W., Hung Y-J., Hwang MY., Hwu C-M., Ichihara S., Isono M., Jang H-M., Jiang G., Jonas JB., Kamatani Y., Katsuya T., Kawaguchi T., Khor C-C., Kohara K., Lee M-S., Lee NR., Li L., Liu J., Luk AO., Lv J., Okada Y., Pereira MA., Sabanayagam C., Shi J., Shin DM., So WY., Takahashi A., Tomlinson B., Tsai F-J., van Dam RM., Xiang Y-B., Yamamoto K., Yamauchi T., Yoon K., Yu C., Yuan J-M., Zhang L., Zheng W., Igase M., Cho YS., Rotter JI., Wang Y-X., Sheu WHH., Yokota M., Wu J-Y., Cheng C-Y., Wong T-Y., Shu X-O., Kato N., Park K-S., Tai E-S., Matsuda F., Koh W-P., Ma RCW., Maeda S., Millwood IY., Lee J., Kadowaki T., Walters RG., Kim B-J., Mohlke KL., Sim X.
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.