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

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

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Title: Genome-Wide Association Studies of Asthma in Population-Based Cohorts Confirm Known and Suggested Loci and Identify an Additional Association near HLA
Author: Ramasamy, Adaikalavan; Kuokkanen, Mikko; Vedantam, Sailaja; Gajdos, Zofia Katherine; Couto Alves, Alexessander; Lyon, Helen N.; Ferreira, Manuel A. R.; Strachan, David P.; Zhao, Jing Hua; Abramson, Michael J.; Brown, Matthew A.; Coin, Lachlan; Dharmage, Shyamali C.; Duffy, David L.; Haahtela, Tari; Heath, Andrew C.; Janson, Christer; Kähönen, Mika; Khaw, Kay-Tee; Laitinen, Jaana; Le Souef, Peter; Lehtimäki, Terho; Madden, Pamela A. F.; Marks, Guy B.; Martin, Nicholas G.; Matheson, Melanie C.; Palmer, Cameron Douglas; Palotie, Aarno; Pouta, Anneli; Robertson, Colin F.; Viikari, Jorma; Widen, Elisabeth; Wjst, Matthias; Jarvis, Deborah L.; Montgomery, Grant W.; Thompson, Philip J.; Wareham, Nick; Eriksson, Johan; Jousilahti, Pekka; Laitinen, Tarja; Pekkanen, Juha; Raitakari, Olli T.; O'Connor, George T.; Salomaa, Veikko; Jarvelin, Marjo-Riitta; Hirschhorn, Joel Naom

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Citation: Ramasamy, Adaikalavan, Mikko Kuokkanen, Sailaja Vedantam, Zofia K. Gajdos, Alexessander Couto Alves, Helen N. Lyon, Manuel A. R. Ferreira, et al. 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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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<5x\(10^{−8}\)) 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 (\(P_{Stage1+Stage2}\) = 1.1x\(10^{−9}\)), which is correlated with a variant recently shown to be associated with asthma (rs3771180), and rs9268516 in the HLA region (\(P_{Stage1+Stage2}\) = 1.1x\(10^{−8}\)), 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.
Published Version: doi:10.1371/journal.pone.0044008
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3461045/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10522882
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