Adult onset asthma and interaction between genes and active tobacco smoking : The GABRIEL consortium
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID 3770969
Author(s) Vonk, J. M.; Scholtens, S.; Postma, D. S.; Moffatt, M. F.; Jarvis, D.; Ramasamy, A.; Wjst, M.; Omenaas, E. R.; Bouzigon, E.; Demenais, F.; Nadif, R.; Siroux, V.; Polonikov, A. V.; Solodilova, M.; Ivanov, V. P.; Curjuric, I.; Imboden, M.; Kumar, A.; Probst-Hensch, N.; Ogorodova, L. M.; Puzyrev, V. P.; Bragina, E. Yu; Freidin, M. B.; Nolte, I. M.; Farrall, A. M.; Cookson, W. O. C. M.; Strachan, D. P.; Koppelman, G. H.; Boezen, H. M.
Author(s) at UniBasel Probst Hensch, Nicole
Year 2017
Title Adult onset asthma and interaction between genes and active tobacco smoking : The GABRIEL consortium
Journal PLoS ONE
Volume 12
Number 3
Pages / Article-Number e0172716
Mesh terms Adult; Asthma, genetics; Cohort Studies; Gene-Environment Interaction; Genetic Predisposition to Disease, genetics; Genome-Wide Association Study; Humans; Polymorphism, Single Nucleotide; Smoking, adverse effects
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.
Publisher Public Library of Science
ISSN/ISBN 1932-6203
Full Text on edoc Available
Digital Object Identifier DOI 10.1371/journal.pone.0172716
PubMed ID
ISI-Number WOS:000396011300029
Document type (ISI) Article

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