Genome-wide association study of lung function decline in adults with and without asthma

Imboden, M. and Bouzigon, E. and Curjuric, I. and Ramasamy, A. and Kumar, A. and Hancock, D. B. and Wilk, J. B. and Vonk, J. M. and Thun, G. A. and Siroux, V. and Nadif, R. and Monier, F. and Gonzalez, J. R. and Wjst, M. and Heinrich, J. and Loehr, L. R. and Franceschini, N. and North, K. E. and Altmüller, J. and Koppelman, G. H. and Guerra, S. and Kronenberg, F. and Lathrop, M. and Moffatt, M. F. and O'Connor, G. T. and Strachan, D. P. and Postma, D. S. and London, S. J. and Schindler, C. and Kogevinas, M. and Kauffmann, F. and Jarvis, D. L. and Demenais, F. and Probst-Hensch, N. M.. (2012) Genome-wide association study of lung function decline in adults with and without asthma. Journal of allergy and clinical immunology, 129 (5). pp. 1218-1228.

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Official URL: http://edoc.unibas.ch/dok/A6094193

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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 FEV(1) 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 FEV(1) and FEV(1)/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 FEV(1) decrease suggested for nonasthmatic participants in the discovery phase was replicated (discovery, P = 4.8 x 10(-6); replication, P = .03), and additional sensitivity analyses point to a relation to growth. The top ranking signal, TUSC3, which is associated with FEV(1)/FVC ratio decrease in asthmatic participants (P = 5.3 x 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
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Chronic Disease Epidemiology
UniBasel Contributors:Probst Hensch, Nicole and Imboden, Medea and Schindler, Christian and Curjuric, Ivan
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:03 May 2018 09:39
Deposited On:16 Aug 2013 07:28

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