No association between DNA methylation and COPD in never and current smokers

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory lung disease with cigarette smoke as the main risk factor for its development. Since not every smoker develops COPD, other factors likely underlie differences in susceptibility to develop COPD. Here, we tested if DNA methylation may be such a factor by assessing the association between DNA methylation levels and COPD in never and current smokers from the general population. METHODS: For the current study, 1561 subjects were non-randomly selected from the LifeLines cohort study. We included 903 never smokers and 658 current smokers with and without COPD, defined as pre-bronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV(1)/FVC) <70%. Subsequently, we performed robust regression analysis on whole blood DNA methylation levels of 420 938 CpG sites with COPD as outcome. RESULTS: None of the CpG sites in both the never and the current smokers were genome-wide significantly associated with COPD. CpG site cg14972228 annotated to SIPAL3 was most significant (p=5.66×10(−6)) in the never smokers, while CpG site cg08282037 annotated to EPS8L1 was most significant (p=1.45×10(−5)) in the current smokers. CONCLUSION: In contrast to a previous, smaller study, we did not observe any significant association between DNA methylation levels and the presence of COPD, independent of smoking status. Apparently, DNA methylation studies are highly variable.