PT - JOURNAL ARTICLE 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 TI - Heritability and genome-wide association study of diffusing capacity of the lung AID - 10.1101/277343 DP - 2018 Jan 01 TA - bioRxiv PG - 277343 4099 - http://biorxiv.org/content/early/2018/04/09/277343.short 4100 - http://biorxiv.org/content/early/2018/04/09/277343.full AB - 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 GPR126 that is significantly associated with DLCO/VA. Gene expression analysis of GPR126 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 GPR126 gene region was significantly associated with DLCO/VA. Pulmonary GPR126 expression was decreased in patients with COPD.