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Article: Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype

TitleGenome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype
Authors
KeywordsRhinitis
atopy
selection
single nucleotide polymorphism
bivariate
genetic correlation
Issue Date2014
Citation
Journal of Allergy and Clinical Immunology, 2014, v. 133, n. 6, p. 1564-1571 How to Cite?
AbstractBackground To date, no genome-wide association study (GWAS) has considered the combined phenotype of asthma with hay fever. Previous analyses of family data from the Tasmanian Longitudinal Health Study provide evidence that this phenotype has a stronger genetic cause than asthma without hay fever. Objective We sought to perform a GWAS of asthma with hay fever to identify variants associated with having both diseases. Methods We performed a meta-analysis of GWASs comparing persons with both physician-diagnosed asthma and hay fever (n = 6,685) with persons with neither disease (n = 14,091). Results At genome-wide significance, we identified 11 independent variants associated with the risk of having asthma with hay fever, including 2 associations reaching this level of significance with allergic disease for the first time: ZBTB10 (rs7009110; odds ratio [OR], 1.14; P = 4 × 10-9) and CLEC16A (rs62026376; OR, 1.17; P = 1 × 10-8). The rs62026376:C allele associated with increased asthma with hay fever risk has been found to be associated also with decreased expression of the nearby DEXI gene in monocytes. The 11 variants were associated with the risk of asthma and hay fever separately, but the estimated associations with the individual phenotypes were weaker than with the combined asthma with hay fever phenotype. A variant near LRRC32 was a stronger risk factor for hay fever than for asthma, whereas the reverse was observed for variants in/near GSDMA and TSLP. Single nucleotide polymorphisms with suggestive evidence for association with asthma with hay fever risk included rs41295115 near IL2RA (OR, 1.28; P = 5 × 10-7) and rs76043829 in TNS1 (OR, 1.23; P = 2 × 10-6). Conclusion By focusing on the combined phenotype of asthma with hay fever, variants associated with the risk of allergic disease can be identified with greater efficiency. © 2014 American Academy of Allergy, Asthma & Immunology.
Persistent Identifierhttp://hdl.handle.net/10722/221362
ISSN
2015 Impact Factor: 12.485
2015 SCImago Journal Rankings: 5.513

 

DC FieldValueLanguage
dc.contributor.authorFerreira, Manuel A R-
dc.contributor.authorMatheson, Melanie C.-
dc.contributor.authorTang, Clara S.-
dc.contributor.authorGranell, Raquel-
dc.contributor.authorAng, Wei-
dc.contributor.authorHui, Jennie-
dc.contributor.authorKiefer, Amy K.-
dc.contributor.authorDuffy, David L.-
dc.contributor.authorBaltic, Svetlana-
dc.contributor.authorDanoy, Patrick-
dc.contributor.authorBui, Minh-
dc.contributor.authorPrice, Loren-
dc.contributor.authorSly, Peter D.-
dc.contributor.authorEriksson, Nicholas-
dc.contributor.authorMadden, Pamela A.-
dc.contributor.authorAbramson, Michael J.-
dc.contributor.authorHolt, Patrick G.-
dc.contributor.authorHeath, Andrew C.-
dc.contributor.authorHunter, Michael-
dc.contributor.authorMusk, Bill-
dc.contributor.authorRobertson, Colin F.-
dc.contributor.authorLe Souëf, Peter-
dc.contributor.authorMontgomery, Grant W.-
dc.contributor.authorHenderson, A. John-
dc.contributor.authorTung, Joyce Y.-
dc.contributor.authorDharmage, Shyamali C.-
dc.contributor.authorBrown, Matthew A.-
dc.contributor.authorJames, Alan-
dc.contributor.authorThompson, Philip J.-
dc.contributor.authorPennell, Craig-
dc.contributor.authorMartin, Nicholas G.-
dc.contributor.authorEvans, David M.-
dc.contributor.authorHinds, David A.-
dc.contributor.authorHopper, John L.-
dc.date.accessioned2015-11-18T06:09:06Z-
dc.date.available2015-11-18T06:09:06Z-
dc.date.issued2014-
dc.identifier.citationJournal of Allergy and Clinical Immunology, 2014, v. 133, n. 6, p. 1564-1571-
dc.identifier.issn0091-6749-
dc.identifier.urihttp://hdl.handle.net/10722/221362-
dc.description.abstractBackground To date, no genome-wide association study (GWAS) has considered the combined phenotype of asthma with hay fever. Previous analyses of family data from the Tasmanian Longitudinal Health Study provide evidence that this phenotype has a stronger genetic cause than asthma without hay fever. Objective We sought to perform a GWAS of asthma with hay fever to identify variants associated with having both diseases. Methods We performed a meta-analysis of GWASs comparing persons with both physician-diagnosed asthma and hay fever (n = 6,685) with persons with neither disease (n = 14,091). Results At genome-wide significance, we identified 11 independent variants associated with the risk of having asthma with hay fever, including 2 associations reaching this level of significance with allergic disease for the first time: ZBTB10 (rs7009110; odds ratio [OR], 1.14; P = 4 × 10-9) and CLEC16A (rs62026376; OR, 1.17; P = 1 × 10-8). The rs62026376:C allele associated with increased asthma with hay fever risk has been found to be associated also with decreased expression of the nearby DEXI gene in monocytes. The 11 variants were associated with the risk of asthma and hay fever separately, but the estimated associations with the individual phenotypes were weaker than with the combined asthma with hay fever phenotype. A variant near LRRC32 was a stronger risk factor for hay fever than for asthma, whereas the reverse was observed for variants in/near GSDMA and TSLP. Single nucleotide polymorphisms with suggestive evidence for association with asthma with hay fever risk included rs41295115 near IL2RA (OR, 1.28; P = 5 × 10-7) and rs76043829 in TNS1 (OR, 1.23; P = 2 × 10-6). Conclusion By focusing on the combined phenotype of asthma with hay fever, variants associated with the risk of allergic disease can be identified with greater efficiency. © 2014 American Academy of Allergy, Asthma & Immunology.-
dc.languageeng-
dc.relation.ispartofJournal of Allergy and Clinical Immunology-
dc.subjectRhinitis-
dc.subjectatopy-
dc.subjectselection-
dc.subjectsingle nucleotide polymorphism-
dc.subjectbivariate-
dc.subjectgenetic correlation-
dc.titleGenome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype-
dc.typeArticle-
dc.description.natureLink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.jaci.2013.10.030-
dc.identifier.pmid24388013-
dc.identifier.scopuseid_2-s2.0-84901754015-
dc.identifier.hkuros234023-
dc.identifier.volume133-
dc.identifier.issue6-
dc.identifier.spage1564-
dc.identifier.epage1571-
dc.identifier.eissn1097-6825-

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