Genome-Wide Association Studies of Asthma in Population-Based Cohorts Confirm Known and Suggested Loci and Identify an Additional Association near HLA

Year: 2012

Type: article

Abstract: RATIONALE: Asthma has substantial morbidity and mortality and a strong genetic component, but identification of genetic risk factors is limited by availability of suitable studies. OBJECTIVES: To test if population-based cohorts with self-reported physician-diagnosed asthma and genome-wide association (GWA) data could be used to validate known associations with asthma and identify novel associations. METHODS: The APCAT (Analysis in Population-based Cohorts of Asthma Traits) consortium consists of 1,716 individuals with asthma and 16,888 healthy controls from six European-descent population-based cohorts. We examined associations in APCAT of thirteen variants previously reported as genome-wide significant (P<5 x 10(-8)) and three variants reported as suggestive (P<5× 10(-7)). We also searched for novel associations in APCAT (Stage 1) and followed-up the most promising variants in 4,035 asthmatics and 11,251 healthy controls (Stage 2). Finally, we conducted the first genome-wide screen for interactions with smoking or hay fever. MAIN RESULTS: We observed association in the same direction for all thirteen previously reported variants and nominally replicated ten of them. One variant that was previously suggestive, rs11071559 in RORA, now reaches genome-wide significance when combined with our data (P = 2.4 × 10(-9)). We also identified two genome-wide significant associations: rs13408661 near IL1RL1/IL18R1 (P(Stage1+Stage2) = 1.1x10(-9)), which is correlated with a variant recently shown to be associated with asthma (rs3771180), and rs9268516 in the HLA region (P(Stage1+Stage2) = 1.1x10(-8)), which appears to be independent of previously reported associations in this locus. Finally, we found no strong evidence for gene-environment interactions with smoking or hay fever status. CONCLUSIONS: Population-based cohorts with simple asthma phenotypes represent a valuable and largely untapped resource for genetic studies of asthma.

Source: PLoS ONE

DOI: 10.1371/journal.pone.0044008

Institutions: King's College London, Imperial College London, Finnish Institute for Health and Welfare, Broad Institute, Boston Children's Hospital, QIMR Berghofer Medical Research Institute, University of London, St George's, University of London, Addenbrooke's Hospital, MRC Epidemiology Unit, Monash University, The University of Queensland, Princess Alexandra Hospital, The University of Melbourne, Helsinki University Hospital, Washington University in St. Louis, Uppsala University, Tampere University Hospital, Finnish Institute of Occupational Health, Princess Margaret Hospital for Children, University of Tampere, The University of Sydney, Woolcock Institute of Medical Research, University of Helsinki, Wellcome Sanger Institute, Institute for Molecular Medicine Finland, University of Oulu, Murdoch Children's Research Institute, University of Turku, Helmholtz Munich, The University of Western Australia, Folkhälsans Forskningscentrum, Turku University Hospital, University of Eastern Finland, Boston University, Framingham Heart Study, Harvard University

Language: English

Topic: Asthma and respiratory diseases

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,382

Funders: Mesothelioma Applied Research Foundation, Foundation for Cardiovascular Research, American Asthma Foundation, Wellcome Trust, National Institute for Health and Care Research, European Commission, Academy of Finland, Sydäntutkimussäätiö, Oulun Yliopisto, Diabetestutkimussäätiö, National Institutes of Health, Medical Research Council, National Health and Medical Research Council, Biocenter, University of Oulu, National Institute on Alcohol Abuse and Alcoholism, National Heart, Lung, and Blood Institute, National Institute of Mental Health

OpenAlex ID: W2121029583