Abstract
BACKGROUND: Ambient air pollution is associated with numerous adverse health outcomes, but the underlying mechanisms are not well understood; epigenetic effects including altered DNA methylation could play a role. To evaluate associations of long-term air pollution exposure with DNA methylation in blood, we conducted an epigenome-wide association study in a Korean chronic obstructive pulmonary disease cohort (N = 100 including 60 cases) using Illumina's Infinium HumanMethylation450K Beadchip. Annual average concentrations of particulate matter ≤ 10 μm in diameter (PM(10)) and nitrogen dioxide (NO(2)) were estimated at participants' residential addresses using exposure prediction models. We used robust linear regression to identify differentially methylated probes (DMPs) and two different approaches, DMRcate and comb-p, to identify differentially methylated regions (DMRs). RESULTS: After multiple testing correction (false discovery rate < 0.05), there were 12 DMPs and 27 DMRs associated with PM(10) and 45 DMPs and 57 DMRs related to NO(2). DMP cg06992688 (OTUB2) and several DMRs were associated with both exposures. Eleven DMPs in relation to NO(2) confirmed previous findings in Europeans; the remainder were novel. Methylation levels of 39 DMPs were associated with expression levels of nearby genes in a separate dataset of 3075 individuals. Enriched networks were related to outcomes associated with air pollution including cardiovascular and respiratory diseases as well as inflammatory and immune responses. CONCLUSIONS: This study provides evidence that long-term ambient air pollution exposure impacts DNA methylation. The differential methylation signals can serve as potential air pollution biomarkers. These results may help better understand the influences of ambient air pollution on human health.