Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.
Cho YS., Chen C-H., Hu C., Long J., Ong RTH., Sim X., Takeuchi F., Wu Y., Go MJ., Yamauchi T., Chang Y-C., Kwak SH., Ma RCW., Yamamoto K., Adair LS., Aung T., Cai Q., Chang L-C., Chen Y-T., Gao Y., Hu FB., Kim H-L., Kim S., Kim YJ., Lee JJ-M., Lee NR., Li Y., Liu JJ., Lu W., Nakamura J., Nakashima E., Ng DP-K., Tay WT., Tsai F-J., Wong TY., Yokota M., Zheng W., Zhang R., Wang C., So WY., Ohnaka K., Ikegami H., Hara K., Cho YM., Cho NH., Chang T-J., Bao Y., Hedman ÅK., Morris AP., McCarthy MI., DIAGRAM Consortium None., MuTHER Consortium None., Takayanagi R., Park KS., Jia W., Chuang L-M., Chuang L-M., Chan JCN., Maeda S., Kadowaki T., Lee J-Y., Wu J-Y., Teo YY., Tai ES., Shu XO., Mohlke KL., Kato N., Han B-G., Seielstad M.
We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.