Abstract

Carotid intima-media thickness (IMT) is a measure of atherosclerosis and a predictor of vascular diseases. Traditional vascular risk factors and genetic variants do not completely explain the variation in carotid IMT. We sought to identify epigenetic factors that may contribute to the remaining carotid IMT variability. An epigenome-wide association study was performed in 61 Dominican families with 769 individuals. A cytosine nucleotide that precedes a guanine nucleotide methylation in blood-derived DNA was measured using the Human MethylationEPIC BeadChip. Linear mixed model analyses were performed regressing bifurcation carotid IMT (bIMT) on beta values for cytosine nucleotide that precedes a guanine nucleotide sites, adjusting for covariates, followed by differentially methylated region (DMR) analysis. One-sample Mendelian randomization analysis was conducted to investigate causal associations between DMRs and bIMT. Twenty-five DMRs were associated with bIMT (Sidak Our study and previous expression quantitative trait locus studies provide converging evidence that reduced