East Asian Genome-wide association study derived loci in relation to type 2 diabetes in the Han Chinese population

Meta-analysis of GWAS in East Asian populations had established 10 loci that were associated with type 2 diabetes. Eight of them were with genome-wide significance and two with a border line association. Since these data have not been studied in an independent Han Chinese population, we aimed to investigate the association of these susceptibility loci with type 2 diabetes in an independent Han Chinese population. We executed a case-control study in 2 000 Chinese by the SNPscan method. Firstly, the repetitive sequences of 10 loci were assessed. Next, we investigated the association of 8 SNPs out of 10 with type 2 diabetes and constructed the GRS of those 8 SNPs. Finally, the relationship of the 8 loci and diabetes-related traits was analyzed. Based on the fact, that highly repetitive sequences were detected in 2 SNPs, we investigated the remaining 8 SNPs. With the exception of four SNPs (CMIP rs16955379, PEPD rs3786897, PSMD6 rs831571, ZFAND3 rs9470794), the other SNPs had the same direction of effect (odds ratio [OR]>1.0) as in the original reports, especially GLIS3 rs7041847 and KCNK16 rs1535500 were significantly associated with type 2 diabetes (rs1535500: p=0.005, OR=1.224, 95% CI 1.062-1.409; rs7041847: p=0.035, OR=1.118, 95% CI 1.070-1.388). The GRS constructed from the 8 SNPs was significantly associated with type 2 diabetes in the Chinese population (p=0.004, OR=1.065, 95% CI: 1.021-1.111). Among the participants with 24≤BMI<28 kg/m2 the 8 SNPs were significantly associated with type 2 diabetes (p=0.040, OR=1.079, 95% CI: 1.003-1.160). In quantitative trait analyses, WWOX rs17797882 was associated with decreased HOMA-β and increased level of TG and HDL-Ch, while PEPD rs3786897 and MAEA rs6815464 were associated with decreased fasting plasma glucose, and KCNK16 rs1535500 has shown a significant association with increased T-Ch and PSMD6 rs831571 had a significant association with decreased HDL-Ch. In Conclusion, with high probability the 8 loci identified in the East Asian GWAS meta-analysis are associated with type 2 diabetes in the Han Chinese population.