Epigenome-wide association study on short-, intermediate- and long-term ozone exposure in Han Chinese, the NSPT study

Epidemiological and epigenetic studies have acknowledged ambient ozone exposure associated with inflam-matory and cardiovascular disease. However, the molecular mechanisms still remained unclear, and epigenome-wide analysis in cohort were lacking, especially in Chinese. We included blood-derived DNA methylation for 3365 Chinese participants from the NSPT cohort and estimated individual ozone exposure level of short-, in- termediate-and long-term, based on a validated prediction model. We performed epigenome-wide association studies which identified 59 CpGs and 30 DMRs at a strict genome-wide significance (P < 5 x10(- 8)). We also conducted comparison on the DNA methylation alteration corresponding to different time windows, and observed an enhanced differentiated methylation trend for intermediate-and long-term exposure, while the short-term exposure associated methylation changes did not retain. The targeted genes of methylation alteration were involved in mechanism related to aging, inflammation disease, metabolic syndrome, neurodevelopmental disorders, and oncogenesis. Underlying pathways were enriched in biological activities including telomere maintenance process, DNA damage response and megakaryocyte differentiation. In conclusion, our study is the first EWAS on ozone exposure conducted in large-scale Han Chinese cohort and identified associated DNA methylation change on CpGs and regions, as well as related gene functions and pathways.