A case-control genome-wide association study of metabolic syndrome in Korean

Abstract

Metabolic syndrome (METS) constitutes several metabolic disorders including central obesity, dyslipidemia, glucose intolerances, and elevated blood pressure. METS is known to increase the risk of developing cardiovascular disease and diabetes. Genome-wide association study (GWAS) for 2,657 cases and 5,917 controls in Korean populations was performed to discover the genetic risk factors of METS. As a result, we identified 2 SNPs with genome-wide significance level p-values(<;5×10-8), 8SNPs with genome-wide suggestive p-values (5×10-8≤p-values<;1×10-5), and 2SNPs of more functional variants with borderline p-values (5×10-5≤p-values<;1×10-4). On the other hand, the multiple correction criteria of conventional GWASs exclude false-positive loci, but simultaneously, they discard many true-positive loci. To reconsider the discarded true-positive loci, we attempted to include the functional variants [nonsynonymous SNPs (nsSNPs) and expression quantitative trait loci (eQTL)] among the top 5000 SNPs based on the proportion of phenotypic variance explained by genotypic variance. In total, 159 eQTLs and 18 nsSNPs were presented in the top 5000 SNPs. Although they should be replicated in other independent populations, 6eQTLs and 2nsSNP loci were located in the molecular pathways of LPL, APOA5, and CHRM2, which were the significant or suggestive loci in the METS GWAS. Conclusively, our approach using the conventional GWAS, reconsidering functional variants and pathway-based interpretation, suggests a useful method to understand the GWAS results of complex traits and can be expanded in other genome-wide association studies.