Epigenome-wide association in the METSIM cohort identifies 22 novel loci for diabetes and metabolic syndrome traits

In this study, we examined the association of DNA methylation with metabolic traits in humans using adipose tissue samples from the Metabolic Syndrome in Men (METSIM) cohort. The METSIM cohort has been thoroughly characterized for longitudinal clinical data of metabolic traits including a 3-point oral glucose tolerance test, cardiovascular disorders, diabetes complications, drug and diet questionnaire, as well as high density genotyping, and genome-wide expression in adipose. We performed epigenome-wide association studies on clinical traits using reduced representation bisulfite sequencing data and identified 61 signifiant associations for metabolic syndrome traits, corresponding to 25 unique loci. These associations include previously known genes, FASN, RXRA, MSH2, and MSH6, as well as 22 loci harboring 18 new candidate genes for diabetes and obesity in humans. Genomic DNA human adipose tissue samples was analyzed with respect to cytosine methylation levels using reduced-representation bisulfite sequencing. The raw and processed data submitted here represents all 205 samples used in the analysis.