Epigenome-wide association study on diffusing capacity of the lung (DLCO)

Background Epigenetics may play an important role in pathogenesis of lung diseases. However, little is known about the epigenetic factors that influence impaired gas exchange at the lungs. Aim To identify the epigenetic signatures of the diffusing capacity of the lung measured by carbon monoxide uptake. Methods Epigenome-Wide Association Study (EWAS) was performed on diffusing capacity, measured by carbon monoxide uptake (DLCO) and per alveolar volume (DLCO /VA) using the single-breath technique in 2674 individuals from two population-based cohort studies, the Rotterdam Study (the discovery panel) and the Framingham Heart Study (the replication panel). We assessed the clinical relevance of our findings by investigating the identified sites in whole blood and lung tissue specific gene expression. Results We identified and replicated two CpG sites (cg05575921 and cg05951221) that were significantly associated with DLCO /VA and one (cg05575921) suggestively associated with DLCO. Furthermore, we found a positive association between AHRR (cg05575921) hypomethylation and gene expression of EXOC3 in whole blood. We confirmed that the expression of EXOC3 in lung tissue is positively associated with DLCO/VA and DLCO. Conclusions We report on epigenome wide associations with diffusing capacity in the general population. Our results suggest EXOC3 to be an excellent candidate through which smoking induced hypomethylation of AHRR might affect pulmonary gas exchange.