Findings from the first wave of candidate gene methylation studies for smoking (approximately 2008–2012), generally using bisulfite pyrosequencing or mass spectrometry, established the existence of differences in methylation between cases and controls at the promoters of several candidate genes for smoking, including MAO-A and MAO-B. Two early studies by Philibert and colleagues [35,36] found that symptom counts for nicotine dependence were associated with decreased methylation at the MAO-A promoter, that genotype and sex-specific effects influenced methylation, and that changes in methylation pattern persisted over time after smoking cessation. There also did not appear to be a significant difference between methylation patterns in whole blood samples versus transformed lymphoblasts. Launay and colleagues [37] similarly found a decrease in MAO-B promoter methylation in peripheral blood mononuclear cells (PBMCs) due to smoking. At another candidate gene for smoking, catechol-O-methyltransferase (COMT), specific CpGs showed differential methylation in smokers versus nonsmokers, with a delta beta of approximately 6% at the site with the greatest difference [38]. This study was done in an African-American (AA) population, highlighting the need to replicate findings to establish generalizability across differing ethnic groups.
