PM_2.5-related DNA methylation and the association with lung function in non-smokers

PM_2.5 exposure leads to lung function alteration. The potential pathway underlying above association, especially the role of DNA methylation is unclear. The objectives of this study are to evaluate the associations of personal PM_2.5 concentrations with DNA methylation at the epigenome-wide level, and investigate how PM_2.5-related DNA methylation affects lung function. A total of 402 observations of non-smokers were selected from the Wuhan-Zhuhai cohort. PM_2.5 exposure was estimated through a model established in the same population. Blood DNA methylation levels were determined through Illumina Infinium MethylationEPIC BeadChips. Lung function was tested through spirometry on the day of blood sampling. The associations of PM_2.5 exposure with DNA methylation and DNA methylation with lung function were determined through linear mixed models. Ten PM_2.5-related CpG sites (mapped to 7 different genes) were observed with false discovery rate <0.05. Methylation levels of cg24821877, cg24862131, cg23530876, cg11149743 and cg10781276 were positively associated with PM_2.5 concentrations. While methylation levels of cg10314909, cg08968107, cg18362281, cg24663971 and cg17834632 were negatively associated with PM_2.5 concentrations. The top CpG was cg24663971 (P = 1.51✕10^-9). Among the above 10 sites, significantly positive associations of methylation levels of cg24663971 with FVC%pred and FEV₁%pred, and cg10314909 with FVC, FVC%pred, and FEV₁%pred were observed. Age had modification effect on the associations between cg24663971 methylation and FVC%pred, and the associations were more obvious among participants with age ≥58 years. In conclusion, PM_2.5 exposure was associated with DNA methylation, and PM_2.5-related DNA methylation was associated with lung function among Wuhan urban non-smokers.