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

Ramasamy, Adaikalavan, Kuokkanen, Mikko, Vedantam, Sailaja, Gajdos, Zofia K., Alves, Alexessander Couto, 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, Kahonen, Mika, Khaw, Kay-Tee, Laitinen, Jaana, Le Souef, Peter, Lehtimaki, Terho, Madden, Pamela A. F., Marks, Guy B., Martin, Nicholas G., Matheson, Melanie C., Palmer, Cameron D., 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 and Hirschhorn, Joel 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 Article No. e44008: e44008-1-e44008-10. doi:10.1371/journal.pone.0044008


Author Ramasamy, Adaikalavan
Kuokkanen, Mikko
Vedantam, Sailaja
Gajdos, Zofia K.
Alves, Alexessander Couto
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
Kahonen, Mika
Khaw, Kay-Tee
Laitinen, Jaana
Le Souef, Peter
Lehtimaki, Terho
Madden, Pamela A. F.
Marks, Guy B.
Martin, Nicholas G.
Matheson, Melanie C.
Palmer, Cameron D.
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 N.
Title Genome-Wide Association Studies of Asthma in Population-Based Cohorts Confirm Known and Suggested Loci and Identify an Additional Association near HLA
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2012-09-01
Year available 2012
Sub-type Article (original research)
DOI 10.1371/journal.pone.0044008
Open Access Status DOI
Volume 7
Issue 9 Article No. e44008
Start page e44008-1
End page e44008-10
Total pages 10
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Language eng
Subject 1300 Biochemistry, Genetics and Molecular Biology
1100 Agricultural and Biological Sciences
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<5x10) and three variants reported as suggestive (P<5×10). 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). We also identified two genome-wide significant associations: rs13408661 near IL1RL1/IL18R1 (P = 1.1x10), which is correlated with a variant recently shown to be associated with asthma (rs3771180), and rs9268516 in the HLA region (P = 1.1x10), 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.
Formatted 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<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 (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.
Keyword Ror Alpha
Genetics
Health
Lung
Susceptibility
Metaanalysis
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 018996
613627
213506
089062
201413
129287
5R01HL087679-02
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2013 Collection
UQ Diamantina Institute Publications
 
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