TY - JOUR
T1 - Genome-Wide Association Studies of Asthma in Population-Based Cohorts Confirm Known and Suggested Loci and Identify an Additional Association near HLA
AU - Ramasamy, Adaikalavan
AU - Kuokkanen, Mikko
AU - Vedantam, Sailaja
AU - Gajdos, Zofia K.
AU - Couto Alves, Alexessander
AU - Lyon, Helen N.
AU - Ferreira, Manuel A.R.
AU - Strachan, David P.
AU - Zhao, Jing Hua
AU - Abramson, Michael J.
AU - Brown, Matthew A.
AU - Coin, Lachlan
AU - Dharmage, Shyamali C.
AU - Duffy, David L.
AU - Haahtela, Tari
AU - Heath, Andrew C.
AU - Janson, Christer
AU - Kähönen, Mika
AU - Khaw, Kay Tee
AU - Laitinen, Jaana
AU - Le Souef, Peter
AU - Lehtimäki, Terho
AU - Madden, Pamela A.F.
AU - Marks, Guy B.
AU - Martin, Nicholas G.
AU - Matheson, Melanie C.
AU - Palmer, Cameron D.
AU - Palotie, Aarno
AU - Pouta, Anneli
AU - Robertson, Colin F.
AU - Viikari, Jorma
AU - Widen, Elisabeth
AU - Wjst, Matthias
AU - Jarvis, Deborah L.
AU - Montgomery, Grant W.
AU - Thompson, Philip J.
AU - Wareham, Nick
AU - Eriksson, Johan
AU - Jousilahti, Pekka
AU - Laitinen, Tarja
AU - Pekkanen, Juha
AU - Raitakari, Olli T.
AU - O'Connor, George T.
AU - Salomaa, Veikko
AU - Jarvelin, Marjo Riitta
AU - Hirschhorn, Joel N.
PY - 2012/9/28
Y1 - 2012/9/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84866995093&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0044008
DO - 10.1371/journal.pone.0044008
M3 - Article
C2 - 23028483
AN - SCOPUS:84866995093
SN - 1932-6203
VL - 7
JO - PloS one
JF - PloS one
IS - 9
M1 - e44008
ER -