Smoking May Affect Pulmonary Function through DNA Methylation: an Epigenome-Wide Association Study in Korean Men

Smoking is a risk factor for various disease outcomes and is one of the modifiers of DNA methylation. We aimed to identify smoking-related DNA methylation sites (CpG-sites) and test whether one identified CpG-site is associated with smoking-related traits and pulmonary function. We obtained DNA methylation data of 209 men from the Korean Genome and Epidemiology Study analyzed by Illumina's HumanMethylation450 array. To identify smoking-related DNA methylation sites, epigenome-wide association analysis of smoking status was conducted, adjusting for age, area, current drinking status, and body mass index. We assessed the association between smoking intensity and DNA methylation of cg05951221 (AHRR), the CpG showing the strongest largest difference in DNA methylation among the 5 hypomethylated CpGs in current smokers compared to never smokers. The association between DNA methylation and pulmonary function was examined longitudinally resulting in a positive association between DNA methylation and forced expiratory volume in 1 second/forced vital capacity, regardless of adjustment for smoking status. This suggests that DNA methylation associates with long-term pulmonary function. Our study contributes to explaining the relationship between smoking and pulmonary function via DNA methylation.