TY - JOUR T1 - Heritability and genome-wide association study of diffusing capacity of the lung JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.00647-2018 SP - 1800647 AU - Natalie Terzikhan AU - Fangui Sun AU - Fien M. Verhamme AU - Hieab H.H. Adams AU - Daan Loth AU - Ken R. Bracke AU - Bruno H. C. Stricker AU - Lies Lahousse AU - Josée Dupuis AU - Guy G. Brusselle AU - George T. O'Connor Y1 - 2018/01/01 UR - http://erj.ersjournals.com/content/early/2018/07/12/13993003.00647-2018.abstract N2 - Background: Although several genome wide association studies (GWAS) have investigated the genetics of pulmonary ventilatory function, little is known about the genetic factors that influence gas exchange.Aim: To investigate the heritability of, and genetic variants associated with the diffusing capacity of the lung.Methods: GWAS was performed on diffusing capacity, measured by carbon monoxide uptake (DLCO) and per alveolar volume (DLCO/VA) using the single-breath technique, in 8,372 individuals from two population-based cohort studies, the Rotterdam Study and the Framingham Heart Study. Heritability was estimated in related (n=6,246) and unrelated (n=3,286) individuals.Results: Heritability of DLCO and DLCO/VA ranged between 23% and 28% in unrelated individuals and between 45% and 49% in related individuals. Meta-analysis identified a genetic variant in ADGRG6 that is significantly associated with DLCO/VA. Gene expression analysis of ADGRG6 in human lung tissue revealed a decreased expression in patients with COPD and subjects with decreased DLCO/VA.Conclusion: DLCO and DLCO/VA are heritable traits, with a considerable proportion of variance explained by genetics. A functional variant in ADGRG6 gene region was significantly associated with DLCO/VA. Pulmonary ADGRG6 expression was decreased in patients with COPD.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. 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 ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Terzikhan has nothing to disclose.Conflict of interest: Dr. Sun has nothing to disclose.Conflict of interest: Dr. Verhamme has nothing to disclose.Conflict of interest: Dr. Adams has nothing to disclose.Conflict of interest: Dr. Loth has nothing to disclose.Conflict of interest: Dr. Bracke has nothing to disclose.Conflict of interest: Dr. Stricker has nothing to disclose.Conflict of interest: Dr. Lahousse reports personal fees from Boehringer Ingelheim GmbH, personal fees and non-financial support from Novartis , grants from AstraZeneca, grants and non-financial support from European Respiratory Society, grants and non-financial support from Belgian Respiratory Society, grants from Chiesi, outside the submitted work; .Conflict of interest: Dr. Dupuis has nothing to disclose.Conflict of interest: Dr. Brusselle has nothing to disclose.Conflict of interest: Dr. O'Connor reports personal fees from AstraZeneca, grants from Janssen Pharmaceuticals, outside the submitted work; . ER -