Traffic-related air pollution and genome-wide DNA methylation: A randomized, crossover trial

Traffic-related air pollution (TRAP) has been associated with changes in gene-specific DNA methylation. However, few studies have investigated impact of TRAP exposure on genome-wide DNA methylation in circulating blood of human.To explore the association between TRAP exposure and genome-wide DNA methylation.We conducted a randomized, crossover exposure trial among 35 healthy adults in Shanghai, China. All subjects were randomly allocated to a traffic-free park or a main road for consecutive 4 h, respectively. Blood genome-wide DNA methylation after each exposure session was measured by the Infinium Methylation EPIC BeadChip (850K). The differentially methylated CpGs loci associated with TRAP exposure were identified using linear mixed-effect model.The average concentrations of traffic-related air pollutants including black carbon, ultrafine particles, carbon dioxide, and nitrogen dioxide were 2-3 times higher in the road compared to those in the park. Methylation levels of 68 CpG loci were significantly changed (false discovery rate < 0.05) following TRAP exposure, among which 49 were hypermethylated and 19 were hypomethylated. The annotated genes based on the differential CpGs loci were related to pathways in cardiovascular signaling, cytokine signaling, immune response, nervous system signaling, and metabolism.We found that TRAP exposure was associated with DNA methylation in dozens of genes concerning cardiometabolic health. This trial for the first-time profiled genome-wide methylation changes induced by TRAP exposure using the 850K assay, providing epigenetic insights in understanding the cardiometabolic effects of TRAP exposure.