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

作者：Lee Ho Sun; Kim Yongkang; Park Taesung

来源：Scientific Reports, 2018, 8(1): 5701.

DOI：10.1038/s41598-018-23074-2

<jats:title>Abstract</jats:title><jats:p>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 <jats:italic>LPL</jats:italic>; rs3782889 in <jats:italic>MYL2</jats:italic>; and rs11065756 and rs10849915 in <jats:italic>CCDC63</jats:italic>. Using exome chip variants, gene-based analysis of rare variants revealed three genes<jats:italic>, CETP</jats:italic>, <jats:italic>SH2B1</jats:italic>, and <jats:italic>ZFP2</jats:italic>, in the discovery stage, among which only <jats:italic>CETP</jats:italic> 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.</jats:p>

• 出版日期2018-4-9