Methylome-Wide Association Study of Central Adiposity Implicate Genes Involved in Immune and Endocrine Systems

ABSTRACT We conducted a methylome-wide association study to examine associations between DNA methylation in whole blood and central adiposity and body fat distribution, measured as waist circumference, waist- to-hip ratio, and waist-to-height ratio adjusted for body mass index, in 2684 African American adults in the Atherosclerosis Risk in Communities study. We validated significantly associated Cytosine-phosphate-Guanine methylation sites (CpGs) among adults using the Women’s Health Initiative and Framingham Heart Study participants (combined N=5743) and generalized associations in adolescents from The Raine Study (N=820). We identified 11 CpGs that were robustly associated with one or more central adiposity trait in adults and 2 in adolescents, including CpG site associations near TXNIP, ADCY7, SREBF1 , and RAP1GAP2 that had not previously been associated with obesity-related traits.