Genome-wide association studies of asthma in population-based cohorts confirm known and suggested loci and identify an additional association near HLA.

Genome-wide association studies of asthma in population-based cohorts confirm known and suggested loci and identify an additional association near HLA.

<h4>Rationale</h4>Asthma has substantial morbidity and mortality and a strong genetic component, but identification of genetic risk factors is limited by availability of suitable studies.<h4>Objectives</h4>To test if population-based cohorts with self-reported physician-diagn...

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Main Authors: Adaikalavan Ramasamy, Mikko Kuokkanen, Sailaja Vedantam, Zofia K Gajdos, Alexessander Couto Alves, Helen N Lyon, Manuel A R Ferreira, David P Strachan, Jing Hua Zhao, Michael J Abramson, Matthew A Brown, Lachlan Coin, Shyamali C Dharmage, David L Duffy, Tari Haahtela, Andrew C Heath, Christer Janson, Mika Kähönen, Kay-Tee Khaw, Jaana Laitinen, Peter Le Souef, Terho Lehtimäki, Australian Asthma Genetics Consortium Collaborators, Pamela A F Madden, Guy B Marks, Nicholas G Martin, Melanie C Matheson, Cameron D Palmer, Aarno Palotie, Anneli Pouta, Colin F Robertson, Jorma Viikari, Elisabeth Widen, Matthias Wjst, Deborah L Jarvis, Grant W Montgomery, Philip J Thompson, Nick Wareham, Johan Eriksson, Pekka Jousilahti, Tarja Laitinen, Juha Pekkanen, Olli T Raitakari, George T O'Connor, Veikko Salomaa, Marjo-Riitta Jarvelin, Joel N Hirschhorn
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0044008&type=printable
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Summary:<h4>Rationale</h4>Asthma has substantial morbidity and mortality and a strong genetic component, but identification of genetic risk factors is limited by availability of suitable studies.<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Main results</h4>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.<h4>Conclusions</h4>Population-based cohorts with simple asthma phenotypes represent a valuable and largely untapped resource for genetic studies of asthma.
ISSN:1932-6203

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