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

Title: Adult onset asthma and interaction between genes and active tobacco smoking: The GABRIEL consortium
Authors: Vonk, JM
Scholtens, S
Postma, DS
Moffatt, MF
Jarvis, D
Ramasamy, A
Wjst, M
Omenaas, ER
Bouzigon, E
Demenais, F
Nadif, R
Siroux, V
Polonikov, AV
Solodilova, M
Ivanov, VP
Curjuric, I
Imboden, M
Kumar, A
Probst-Hensch, N
Ogorodova, LM
Puzyrev, VP
Bragina, EY
Freidin, MB
Nolte, IM
Farrall, AM
Cookson, WOCM
Strachan, DP
Koppelman, GH
Boezen, HM
Item Type: Journal Article
Abstract: Background 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. Methods 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. Results 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). Conclusions Using two genome-wide interaction approaches, we identified novel polymorphisms in nonannotated intergenic regions on chromosomes 9 and 12, that showed suggestive evidence for interaction with active tobacco smoking in the onset of adult asthma.
Issue Date: 2-Mar-2017
Date of Acceptance: 8-Feb-2017
URI: http://hdl.handle.net/10044/1/54033
DOI: https://dx.doi.org/10.1371/journal.pone.0172716
ISSN: 1932-6203
Publisher: Public Library of Science (PLoS)
Journal / Book Title: PLoS ONE
Volume: 12
Issue: 3
Copyright Statement: © 2017 Vonk et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sponsor/Funder: Commission of the European Communities
Royal Brompton & Harefield NHS Foundation Trust
Wellcome Trust
National Institute for Health Research
National Institute for Health Research
Funder's Grant Number: LSHB-CT-2006-018996
B0479
097117/Z/11/Z
BRU 6279
NF-SI-0512-10126
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
WHOLE-GENOME ASSOCIATION
ENVIRONMENT INTERACTION
CHILDHOOD ASTHMA
HUMAN-DISEASES
LARGE-SCALE
EXPOSURE
DECLINE
EGEA
Adult
Asthma
Cohort Studies
Gene-Environment Interaction
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Polymorphism, Single Nucleotide
Smoking
MD Multidisciplinary
General Science & Technology
Publication Status: Published
Article Number: e0172716
Appears in Collections:Infectious Disease Epidemiology
National Heart and Lung Institute
Faculty of Medicine



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