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Adult onset asthma and interaction between genes and active tobacco smoking : The GABRIEL consortium

Vonk, J. M. and Scholtens, S. and Postma, D. S. and Moffatt, M. F. and Jarvis, D. and Ramasamy, A. and Wjst, M. and Omenaas, E. R. and Bouzigon, E. and Demenais, F. and Nadif, R. and Siroux, V. and Polonikov, A. V. and Solodilova, M. and Ivanov, V. P. and Curjuric, I. and Imboden, M. and Kumar, A. and Probst-Hensch, N. and Ogorodova, L. M. and Puzyrev, V. P. and Bragina, E. Yu and Freidin, M. B. and Nolte, I. M. and Farrall, A. M. and Cookson, W. O. C. M. and Strachan, D. P. and Koppelman, G. H. and Boezen, H. M.. (2017) Adult onset asthma and interaction between genes and active tobacco smoking : The GABRIEL consortium. PLoS ONE, 12 (3). e0172716.

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Abstract

Genome-wide association studies have identified novel genetic associations for asthma, but without taking into account the role of active tobacco smoking. This study aimed to identify novel genes that interact with ever active tobacco smoking in adult onset asthma.; We performed a genome-wide interaction analysis in six studies participating in the GABRIEL consortium following two meta-analyses approaches based on 1) the overall interaction effect and 2) the genetic effect in subjects with and without smoking exposure. We performed a discovery meta-analysis including 4,057 subjects of European descent and replicated our findings in an independent cohort (LifeLines Cohort Study), including 12,475 subjects.; First approach: 50 SNPs were selected based on an overall interaction effect at p<10-4. The most pronounced interaction effect was observed for rs9969775 on chromosome 9 (discovery meta-analysis: ORint = 0.50, p = 7.63*10-5, replication: ORint = 0.65, p = 0.02). Second approach: 35 SNPs were selected based on the overall genetic effect in exposed subjects (p <10-4). The most pronounced genetic effect was observed for rs5011804 on chromosome 12 (discovery meta-analysis ORint = 1.50, p = 1.21*10-4; replication: ORint = 1.40, p = 0.03).; Using two genome-wide interaction approaches, we identified novel polymorphisms in non-annotated intergenic regions on chromosomes 9 and 12, that showed suggestive evidence for interaction with active tobacco smoking in the onset of adult asthma.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Chronic Disease Epidemiology > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch)
03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch)
UniBasel Contributors:Probst Hensch, Nicole
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Public Library of Science
e-ISSN:1932-6203
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:31 Aug 2018 06:38
Deposited On:29 May 2017 11:40

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