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Genome-Wide Association Studies of Asthma in Population-Based Cohorts Confirm Known and Suggested Loci and Identify an Additional Association near HLA
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Ramasamy, Adaikalavan (author)
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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, Christer (author)
- Uppsala universitet,Lungmedicin och allergologi
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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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(creator_code:org_t)
- 2012-09-28
- 2012
- English.
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:9, s. e44008-
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https://uu.diva-port... (primary) (Raw object)
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https://journals.plo...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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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.
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- By the author/editor
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Ramasamy, Adaika ...
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Kuokkanen, Mikko
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Vedantam, Sailaj ...
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Gajdos, Zofia K.
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Alves, Alexessan ...
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Lyon, Helen N.
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show more...
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Ferreira, Manuel ...
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Strachan, David ...
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Zhao, Jing Hua
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Abramson, Michae ...
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Brown, Matthew A ...
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Coin, Lachlan
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Dharmage, Shyama ...
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Duffy, David L.
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Haahtela, Tari
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Heath, Andrew C.
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Janson, Christer
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Kahonen, Mika
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Khaw, Kay-Tee
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Laitinen, Jaana
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Le Souef, Peter
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Lehtimaki, Terho
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Madden, Pamela A ...
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Marks, Guy B.
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Martin, Nicholas ...
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Matheson, Melani ...
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Palmer, Cameron ...
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Palotie, Aarno
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Pouta, Anneli
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Robertson, Colin ...
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Viikari, Jorma
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Widen, Elisabeth
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Wjst, Matthias
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Jarvis, Deborah ...
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Montgomery, Gran ...
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Thompson, Philip ...
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Wareham, Nick
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Eriksson, Johan
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Jousilahti, Pekk ...
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Laitinen, Tarja
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Pekkanen, Juha
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Raitakari, Olli ...
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O'Connor, George ...
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Salomaa, Veikko
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Jarvelin, Marjo- ...
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Hirschhorn, Joel ...
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PLOS ONE
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Uppsala University