TY - JOUR T1 - Epigenome-wide association study on diffusing capacity of the lung (DLCO) JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00567-2020 SP - 00567-2020 AU - Natalie Terzikhan AU - Hanfei Xu AU - Ahmed Edris AU - Ken R. Bracke AU - Fien M. Verhamme AU - Bruno H. C. Stricker AU - Josée Dupuis AU - Lies Lahousse AU - George T. O'Connor AU - Guy G. Brusselle Y1 - 2020/01/01 UR - http://openres.ersjournals.com/content/early/2020/10/01/23120541.00567-2020.abstract N2 - 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.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Dr. Terzikhan reports and expert consultation for Boehringer Ingelheim GmbH and Novartis..Conflict of interest: Dr. Xu has nothing to disclose.Conflict of interest: Dr. Edris has nothing to disclose.Conflict of interest: Dr. Bracke has nothing to disclose.Conflict of interest: Dr. Verhamme has nothing to disclose.Conflict of interest: Dr. Stricker has nothing to disclose.Conflict of interest: Dr. Dupuis reports grants from National Institute of Health (NIH), during the conduct of the study.Conflict of interest: Dr. Lahousse reports personal fees from AstraZeneca, from Chiesi, outside the submitted work; and expert consultation for Boehringer Ingelheim GmbH and Novartis.Conflict of interest: Dr. Brusselle reports personal fees from AstraZeneca, personal fees from Boehringer-Ingelhiem, personal fees from Chiesi, personal fees from GlaxoSmithKline, personal fees from Novartis , personal fees from Teva, outside the submitted work; and Guy G. Brusselle is a member of advisory boards for AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Novartis, Sanofi/Regeneron and Teva.Conflict of interest: Dr. O'Connor reports grants from NIH, during the conduct of the study. ER -