Heritability and genome-wide association study of diffusing capacity of the lung.

Autor: Terzikhan N; Dept of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.; Dept of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands.; These authors contributed equally., Sun F; Dept of Biostatistics, Boston University School of Public Health, Boston, MA, USA.; These authors contributed equally., Verhamme FM; Dept of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.; These authors contributed equally., Adams HHH; Dept of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands.; Dept of Radiology and Nuclear Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands., Loth D; Dept of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands., Bracke KR; Dept of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium., Stricker BHC; Dept of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands., Lahousse L; Dept of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands.; Dept of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.; These authors contributed equally., Dupuis J; Dept of Biostatistics, Boston University School of Public Health, Boston, MA, USA.; These authors contributed equally., Brusselle GG; Dept of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.; Dept of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands.; Dept of Respiratory Medicine, Erasmus MC - University Medical Centre Rotterdam, Rotterdam, The Netherlands.; These authors contributed equally., O'Connor GT; Pulmonary Center, Boston University Schools of Medicine and Public Health, Boston, MA, USA.; These authors contributed equally.
Jazyk: angličtina
Zdroj: The European respiratory journal [Eur Respir J] 2018 Sep 15; Vol. 52 (3). Date of Electronic Publication: 2018 Sep 15 (Print Publication: 2018).
DOI: 10.1183/13993003.00647-2018
Abstrakt: 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 ( D LCO ) and per alveolar volume ( V A ) 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 D LCO and D LCO / V A 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 D LCO / V A 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 D LCO / V A D LCO and D LCO / V A are heritable traits, with a considerable proportion of variance explained by genetics. A functional variant in ADGRG6 gene region was significantly associated with D LCO / V A Pulmonary ADGRG6 expression was decreased in patients with COPD.
Competing Interests: Conflict of interest: L. Lahousse reports personal fees for consultancy from Boehringer Ingelheim GmbH, accommodation support and personal fees for consultancy from Novartis, grants from AstraZeneca, travel grants and accommodation support from European Respiratory Society, grants and accommodation support from Belgian Respiratory Society, and grants from Chiesi, outside the submitted work. Conflict of interest: G.T. O'Connor reports personal fees for consulting regarding medications for asthma and COPD from AstraZeneca, and grants paid to Boston University to study genomics of COPD from Janssen Pharmaceuticals, outside the submitted work.
(Copyright ©ERS 2018.)
Databáze: MEDLINE
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