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Genome-Wide Associa...
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Ramasamy, Adaikalavan
(author)
Genome-Wide Association Studies of Asthma in Population-Based Cohorts Confirm Known and Suggested Loci and Identify an Additional Association near HLA
- Article/chapterEnglish2012
Publisher, publication year, extent ...
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2012-09-28
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Public Library of Science (PLoS),2012
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-185642
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-185642URI
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https://doi.org/10.1371/journal.pone.0044008DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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 x 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 = 2.4x10(-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.
Added entries (persons, corporate bodies, meetings, titles ...)
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Kuokkanen, Mikko
(author)
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Vedantam, Sailaja
(author)
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Gajdos, Zofia K.
(author)
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Alves, Alexessander Couto
(author)
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Lyon, Helen N.
(author)
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Ferreira, Manuel A. R.
(author)
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Strachan, David P.
(author)
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Zhao, Jing Hua
(author)
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Abramson, Michael J.
(author)
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Brown, Matthew A.
(author)
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Coin, Lachlan
(author)
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Dharmage, Shyamali C.
(author)
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Duffy, David L.
(author)
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Haahtela, Tari
(author)
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Heath, Andrew C.
(author)
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Janson, ChristerUppsala universitet,Lungmedicin och allergologi(Swepub:uu)chrisjn
(author)
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Kahonen, Mika
(author)
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Khaw, Kay-Tee
(author)
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Laitinen, Jaana
(author)
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Le Souef, Peter
(author)
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Lehtimaki, Terho
(author)
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Madden, Pamela A. F.
(author)
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Marks, Guy B.
(author)
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Martin, Nicholas G.
(author)
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Matheson, Melanie C.
(author)
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Palmer, Cameron D.
(author)
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Palotie, Aarno
(author)
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Pouta, Anneli
(author)
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Robertson, Colin F.
(author)
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Viikari, Jorma
(author)
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Widen, Elisabeth
(author)
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Wjst, Matthias
(author)
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Jarvis, Deborah L.
(author)
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Montgomery, Grant W.
(author)
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Thompson, Philip J.
(author)
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Wareham, Nick
(author)
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Eriksson, Johan
(author)
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Jousilahti, Pekka
(author)
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Laitinen, Tarja
(author)
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Pekkanen, Juha
(author)
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Raitakari, Olli T.
(author)
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O'Connor, George T.
(author)
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Salomaa, Veikko
(author)
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Jarvelin, Marjo-Riitta
(author)
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Hirschhorn, Joel N.
(author)
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Uppsala universitetLungmedicin och allergologi
(creator_code:org_t)
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In:PLOS ONE: Public Library of Science (PLoS)7:9, s. e44008-1932-6203
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Ramasamy, Adaika ...
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Kuokkanen, Mikko
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Gajdos, Zofia K.
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Lyon, Helen N.
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Matheson, Melani ...
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