New Common and Rare Variants Influencing Metabolic Syndrome and Its Individual Components in a Korean Population

To identify novel loci for susceptibility to MetS, we conducted genome-wide association and exome wide association studies consisting of a discovery stage cohort (KARE, 1946 cases and 6427 controls), and a replication stage cohort (HEXA, 430 cases and 3,264 controls). For finding genetic variants for MetS, with its components, we performed multivariate analysis for common and rare associations, using a standard logistic regression analysis for MetS. From the discovery and replication GWA studies, we confirmed 21 genome-wide signals significantly associated with MetS. Of these 21, four were previously unreported to associate with any MetS components: rs765547 near LPL; rs3782889 in MYL2; and rs11065756 and rs10849915 in CCDC63. Using exome chip variants, gene-based analysis of rare variants revealed three genes, CETP, SH2B1, and ZFP2, in the discovery stage, among which only CETP was confirmed in the replication stage. Finally, CETP D442G (rs2303790) associated, as a less common variant, with decreased risk of MetS. In conclusion, we discovered a total of five new MetS-associated loci, and their overlap with other disease-related components, suggest roles in the various etiologies of MetS, and its possible preventive strategies.