title: Adult onset asthma and interaction between genes and active tobacco smoking: The GABRIEL consortium.
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 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.
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands.|University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands.
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authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands.
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authors.lastname: Scholtens
authors.affiliation: University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands.|University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen, the Netherlands.
authors.forename: D S
authors.initials: DS
authors.lastname: Postma
authors.affiliation: Division of Respiratory Sciences, Imperial College, London, United Kingdom.
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authors.affiliation: Population Health and Occupational Disease, Imperial College, London, United Kingdom.|MRC-PHE Centre for Environment and Health, Imperial College, London, United Kingdom.
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authors.lastname: Jarvis
authors.affiliation: Population Health and Occupational Disease, Imperial College, London, United Kingdom.
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authors.affiliation: Institute of Medical Statistics and Epidemiology (IMSE), Klinikum Rechts der Isar, Technical University, Munich, Germany.|Comprehensive Pneumology Center (CPC), Institute of Lung Biology and Disease (iLBD), Helmholtz Center Munich, Neuherberg, Germany.
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authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France.|INSERM, UMR-946, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Bouzigon
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France.|INSERM, UMR-946, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Demenais
authors.affiliation: INSERM, U1168, VIMA: Aging and chronic diseases, Epidemiological and public health approaches, Villejuif, France.|Univ Versailles St-Quentin-en-Yvelines, UMR-S 1168, Montigny le Bretonneux, France.
authors.forename: R
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authors.affiliation: INSERM, IAB, Team of Environmental Epidemiology applied to Reproduction and Respiratory Health, Grenoble, France.|Univ. Grenoble Alpes, IAB, Team of Environmental Epidemiology applied to Reproduction and Respiratory Health, Grenoble, France.|CHU de Grenoble, IAB, Team of Environmental Epidemiology applied to Reproduction and Respiratory Health, Grenoble, France.
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authors.affiliation: Kursk State Medical University, Department of Biology, Medical Genetics and Ecology, Kursk, Russian Federation.
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authors.affiliation: Kursk State Medical University, Department of Biology, Medical Genetics and Ecology, Kursk, Russian Federation.
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authors.affiliation: Kursk State Medical University, Department of Biology, Medical Genetics and Ecology, Kursk, Russian Federation.
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authors.affiliation: Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Basel, Switzerland.
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authors.affiliation: Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Basel, Switzerland.
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authors.affiliation: Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Basel, Switzerland.|Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
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authors.initials: A
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authors.affiliation: Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Basel, Switzerland.
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authors.affiliation: Siberian State Medical University, Tomsk, Russia.
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authors.affiliation: Siberian State Medical University, Tomsk, Russia.|Research Institute of Medical Genetics, Tomsk NRMC, Russia.
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authors.affiliation: Research Institute of Medical Genetics, Tomsk NRMC, Russia.
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authors.affiliation: Research Institute of Medical Genetics, Tomsk NRMC, Russia.
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authors.lastname: Freidin
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands.
authors.forename: I M
authors.initials: IM
authors.lastname: Nolte
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
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authors.affiliation: Division of Respiratory Sciences, Imperial College, London, United Kingdom.
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authors.affiliation: Population Health Research Institute, St George's, University of London, London, United Kingdom.
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authors.initials: DP
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authors.affiliation: University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands.|University of Groningen, University Medical Center Groningen, Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, Groningen, the Netherlands.
authors.forename: G H
authors.initials: GH
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authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands.|University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands.
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mesh_terms: D000328:Adult; D001249:Asthma / Q000139:chemically induced* / Q000235:genetics*; D015331:Cohort Studies; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000009:adverse effects*