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Ramasamy, A.* ; Kuokkanen, M.* ; Vedantam, S.* ; Gajdos, Z.K.* ; Couto Alves, A.* ; Lyon, H.N.* ; Ferreira, M.A.* ; 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.* ; Australian Asthma Genetics Consortium (AAGC) (*) ; Madden, P.A.* ; 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.J.* ; Eriksson, J.* ; Jousilahti, P.* ; Laitinen, T.* ; Pekkanen, J.* ; Raitakari, O.T.* ; O'Connor, G.T.* ; Salomaa, V.* ; Jarvelin, M.R.* ; Hirschhorn, J.N.*

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:e44008 (2012)

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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.

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