Genome-wide association study of lung function decline in adults with and without asthma - 28/04/12
Abstract |
Background |
Genome-wide association studies have identified determinants of chronic obstructive pulmonary disease, asthma, and lung function level; however, none have addressed decline in lung function.
Objective |
We conducted the first genome-wide association study on the age-related decrease in FEV1 and its ratio to forced vital capacity (FVC) stratified a priori by asthma status.
Methods |
Discovery cohorts included adults of European ancestry (1,441 asthmatic and 2,677 nonasthmatic participants: the Epidemiological Study on the Genetics and Environment of Asthma, the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults, and the European Community Respiratory Health Survey). The associations of FEV1 and FEV1/FVC ratio decrease with 2.5 million single nucleotide polymorphisms (SNPs) were estimated. Thirty loci were followed up by in silico replication (1,160 asthmatic and 10,858 nonasthmatic participants: Atherosclerosis Risk in Communities, the Framingham Heart Study, the British 1958 Birth Cohort, and the Dutch Asthma Study).
Results |
Main signals identified differed between asthmatic and nonasthmatic participants. None of the SNPs reached genome-wide significance. The association between the height-related gene DLEU7 and FEV1 decrease suggested for nonasthmatic participants in the discovery phase was replicated (discovery, P = 4.8 × 10−6; replication, P = .03), and additional sensitivity analyses point to a relation to growth. The top ranking signal, TUSC3, which is associated with FEV1/FVC ratio decrease in asthmatic participants (P = 5.3 × 10−8), did not replicate. SNPs previously associated with cross-sectional lung function were not prominently associated with decline.
Conclusions |
Genetic heterogeneity of lung function might be extensive. Our results suggest that genetic determinants of longitudinal and cross-sectional lung function differ and vary by asthma status.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, cohort studies, genome-wide association, lung function decline, heterogeneity
Abbreviations used : ARIC, B58C, COPD, ECRHS, EGEA, FHS, FVC, GWAS, SAPALDIA, SNP
Plan
Information on support for this research is provided in the acknowledgments section of this article. |
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Disclosure of potential conflict of interest: J. B. Wilk has received research support from the National Institutes of Health/National Heart, Lung, and Blood Institute and the Flight Attendant Medical Research Institute. G. H. Koppelman has received research support from the Netherlands Asthma Foundation. D. S. Postma is a consultant for Nycomed and has received research support from the Top Institute Pharma and AstraZeneca. F. Kauffmann has received research support from the French Agency of Research, French Agency for Environmental and Occupational Health and Safety, and INSERM−Ministry of Research “Cohortes et Collections.” The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 129 - N° 5
P. 1218-1228 - mai 2012 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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