Genetic regulation of differentially methylated genes in visceral adipose tissue of severely obese men discordant for the metabolic syndrome

Abstract A genetic influence on methylation levels has been reported and methylation quantitative trait loci (meQTLs) have been identified in various tissues. The contribution of genetic and epigenetic factors in the development of the metabolic syndrome (MetS) has also been noted. In order to pinpoint candidate genes for testing association of SNPs with MetS and its components, we aimed to evaluate the contribution of genetic variations to differentially methylated CpG sites in severely obese men discordant for MetS. Genome-wide differential methylation analysis was conducted in visceral adipose tissue (VAT) of 31 severely obese men discordant for MetS (16 with and 15 without MetS) and identified ∼17,800 variable CpG sites. Genome-wide association study conducted to identify SNPs (meQTL) associated with methylation levels at variable CpG sites revealed 2292 significant associations ( P