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 - 10.1183/13993003.00647-2018 DP - 2018 Sep 01 TA - European Respiratory Journal PG - 1800647 VI - 52 IP - 3 4099 - http://erj.ersjournals.com/content/52/3/1800647.short 4100 - http://erj.ersjournals.com/content/52/3/1800647.full SO - Eur Respir J2018 Sep 01; 52 AB - 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. The aim of the study was to investigate the heritability of, and genetic variants associated with the diffusing capacity of the lung.GWAS was performed on diffusing capacity of the lung measured by carbon monoxide uptake (DLCO) and per alveolar volume (VA) using the single-breath technique, in 8372 individuals from two population-based cohort studies, the Rotterdam Study and the Framingham Heart Study. Heritability was estimated in related (n=6246) and unrelated (n=3286) individuals.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 chronic obstructive pulmonary disease (COPD) and subjects with decreased DLCO/VA.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.This is the first population-based heritability and GWAS study of gas exchange. We identified a functional variant in ADGRG6, and demonstrated differential expression in lung tissue of patients with COPD and decreased diffusing capacity. http://ow.ly/Rvy430kHIT4