Discovery and Replication of HDL-Associated Loci in the Korean Population Using 35,000 Individuals

Abstract

Low levels of HDL are known to be associated with increased risk of type 2 diabetes. It has been suggested as a new therapeutic approach that increase HDL levels in plasma. Previously, to identify lipids traits associated loci, we performed large-scale genome-wide meta-analyses comprising 25,923 East Asian individuals from 11 studies from Korea, Japan, Philippines, China, Singapore, and Taiwan in the discovery stage. With subsequent replication study, we have revealed seven novel loci associated with HDL including loci at CD163-APOBEC1, NCOA2, and NID2-PTGDR. However, previous study was limited in sample size in the discovery stage and low association mapping resolution due to HapMap based imputation analysis. In this study, we performed genome-wide association analyses (GWAS) on HDL using about 35,000 Korean samples and imputed based on 1,000 Genomes project phase 3 and Korean Reference Genome. We focused on imputed (imputation quality score >0.4) and genotyped common variants with minor allele frequency >= 1%. In this discovery study, 17 known loci were replicated at the genome-wide significance level (P<5x10-8). However, no novel association meet the genome-wide significance. We further examined associated loci at suggestive statistical significance (P<5x10-6). As a result, 11 known loci were additionally replicated and 10 possible novel candidate loci were identified including a variant near GATA4. It is noteworthy that the variant near GATA4 was previously reported to be associated with triglyceride level. In summary, we performed a GWAS on HDL using about 35,000 Korean samples. The GWAS confirmed 28 known loci and discovered 10 possible novel candidate loci responsible for variation of HDL level. However, a replication study in an independent cohort is warranted for validating the results. Taken together, the possible novel candidates discovered from this study may provide potential novel therapeutic targets for diseases associated with HDL. Disclosure B. Kim: None. Y. Kim: None. M. Hwang: None. S. Moon: None.