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

Ramasamy, A., Kuokkanen, M., Vedantam, S., Gajdos, Z. K., Couto Alves, A., Lyon, H. N., Ferreira, M. A. R., Strachan, D. P., Zhao, J. H., Abramson, M. J., Brown, M. A., Coin, L., Dharmage, S. C., Duffy, D. L., Haahtela, T., Heath, A. C., Janson, C., Kähönen, M., Khaw, K. T., Laitinen, J., Le Souef, P., Lehtimäki, T., Madden, P. A. F., Marks, G. B., Martin, N. G., Matheson, M. C., Palmer, C. D., Palotie, A., Pouta, A., Robertson, C. F., Viikari, J., Widen, E., Wjst, M., Jarvis, D. L., Montgomery, G. W., Thompson, P. J., Wareham, N., Eriksson, J., Jousilahti, P., Laitinen, T., Pekkanen, J., Raitakari, O. T., O'Connor, G. T., Salomaa, V., Jarvelin, M. R., & Hirschhorn, J. N. (2012) Genome-Wide Association Studies of Asthma in Population-Based Cohorts Confirm Known and Suggested Loci and Identify an Additional Association near HLA. PLoS ONE, 7(9), e44008.

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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<5x10-8) 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 (PStage1+Stage2 = 1.1x10-9), which is correlated with a variant recently shown to be associated with asthma (rs3771180), and rs9268516 in the HLA region (PStage1+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. © 2012 Ramasamy et al.

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ID Code: 87622
Item Type: Journal Article
Refereed: Yes
Additional Information: Read correction via 'Related work' link
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Keywords: article, asthma, cohort analysis, controlled study, gene interaction, gene locus, genetic association, genetic identification, genotype environment interaction, heredity, HLA system, human, morbidity, mortality, phenotype, population based case control study, risk factor, single nucleotide polymorphism, adult, genetic predisposition, genetics, middle aged, quantitative trait locus, HLA antigen, Cohort Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, HLA Antigens, Humans, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Risk Factors
DOI: 10.1371/journal.pone.0044008
ISSN: 19326203 (ISSN)
Divisions: Current > Schools > School of Biomedical Sciences
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2012 Ramasamy et al.
Copyright Statement: 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.
Deposited On: 21 Sep 2015 06:53
Last Modified: 05 Apr 2017 02:17

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