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Article Dans Une Revue PLoS ONE Année : 2017

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

1 University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen
2 Groningen Research Institute for Asthma and COPD
3 Department of Pulmonary Diseases & Tuberculosis [Groningen]
4 Imperial College
5 Imperial College, UK
6 MRC-PHE Centre for Environment and Health, Imperial College, London
7 Population Health and Occupational Disease, Imperial College, London
8 Institute of Medical Statistics and Epidemiology (IMSE), Klinikum Rechts der Isar, Technical University, Munich
9 CPC -M - Comprehensive Pneumology Center Munich [Munich, Germany]
10 Centre for Clinical Research, Haukeland University Hospital, Bergen
11 Univ Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris
12 U946 - Variabilité Génétique et Maladies Humaines
13 VIMA - Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique
14 Univ. Grenoble Alpes, IAB, Team of Environmental Epidemiology applied to Reproduction and Respiratory Health, Grenoble
15 Kursk State Medical University, Department of Biology, Medical Genetics and Ecology, Kursk
16 Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel
17 University Hospital Basel [Basel]
18 Wellcome Trust Centre for Human Genetics
19 Siberian State Medical University, Tomsk, Russia
20 Research Institute of Medical Genetics, Tomsk NRMC
21 Division of Respiratory Sciences, Imperial College, London
22 Population Health Research Institute, St George's, University of London, London
23 Department of Pediatrics [Groningen]
M F Moffatt
  • Fonction : Auteur

Résumé

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 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.
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Dates et versions

hal-04306121 , version 1 (24-11-2023)

Identifiants

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J M Vonk, S. Scholtens, D S Postma, M F Moffatt, D. Jarvis, et al.. Adult onset asthma and interaction between genes and active tobacco smoking: The GABRIEL consortium. PLoS ONE, 2017, 12 (3), pp.e0172716. ⟨10.1371/journal.pone.0172716⟩. ⟨hal-04306121⟩
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