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dc.contributor.authorSarnowski, Chloé-
dc.contributor.authorSugier, Pierre-Emmanuel-
dc.contributor.authorGranell, Raquel-
dc.contributor.authorJarvis, Debbie-
dc.contributor.authorDizier, Marie-Hélène-
dc.contributor.authorEge, Markus-
dc.contributor.authorImboden, Medea-
dc.contributor.authorLaprise, Catherine-
dc.contributor.authorKhusnutdinova, Elza K.-
dc.contributor.authorFreidin, Maxim B.-
dc.contributor.authorCookson, William O.C.-
dc.contributor.authorMoffatt, Miriam-
dc.contributor.authorLathrop, Mark-
dc.contributor.authorSiroux, Valérie-
dc.contributor.authorOgorodova, Ludmila M.-
dc.contributor.authorKarunas, Alexandra S.-
dc.contributor.authorJames, Alan-
dc.contributor.authorProbst-Hensch, Nicole M.-
dc.contributor.authorvon Mutius, Erika-
dc.contributor.authorPin, Isabelle-
dc.contributor.authorKogevinas, Manolis-
dc.contributor.authorHenderson, John-
dc.contributor.authorDemenais, Florence-
dc.contributor.authorBouzigon, Emmanuelle-
dc.date.accessioned2022-03-31T05:33:09Z-
dc.date.available2022-03-31T05:33:09Z-
dc.date.issued2016-04-06-
dc.identifier.urihttps://doi.org/10.1016/j.jaci.2016.03.018-
dc.identifier.urihttp://hdl.handle.net/20.500.12701/1767-
dc.description.abstractBackground Asthma is a heterogeneous disease in which age of onset plays an important role. Objective We sought to identify the genetic variants associated with time to asthma onset (TAO). Methods We conducted a large-scale meta-analysis of 9 genome-wide association studies of TAO (total of 5462 asthmatic patients with a broad range of age of asthma onset and 8424 control subjects of European ancestry) performed by using survival analysis techniques. Results We detected 5 regions associated with TAO at the genome-wide significant level (P < 5 × 10−8). We evidenced a new locus in the 16q12 region (near cylindromatosis turban tumor syndrome gene [CYLD]) and confirmed 4 asthma risk regions: 2q12 (IL-1 receptor–like 1 [IL1RL1]), 6p21 (HLA-DQA1), 9p24 (IL33), and 17q12-q21 (zona pellucida binding protein 2 [ZPBP2]–gasdermin A [GSDMA]). Conditional analyses identified 2 distinct signals at 9p24 (both upstream of IL33) and 17q12-q21 (near ZPBP2 and within GSDMA). Together, these 7 distinct loci explained 6.0% of the variance in TAO. In addition, we showed that genetic variants at 9p24 and 17q12-q21 were strongly associated with an earlier onset of childhood asthma (P ≤ .002), whereas the 16q12 single nucleotide polymorphism was associated with later asthma onset (P = .04). A high burden of disease risk alleles at these loci was associated with earlier age of asthma onset (4 vs 9-12 years, P = 10−4). Conclusion The new susceptibility region for TAO at 16q12 harbors variants that correlate with the expression of CYLD and nucleotide-binding oligomerization domain 2 (NOD2), 2 strong candidates for asthma. This study demonstrates that incorporating the variability of age of asthma onset in asthma modeling is a helpful approach in the search for disease susceptibility genes.ru_RU
dc.language.isoenru_RU
dc.publisherElsevierru_RU
dc.relation.ispartofseriesJournal of Allergy and Clinical Immunology;Volume 138, Issue 4-
dc.subjectAsthmaru_RU
dc.subjectage of onsetru_RU
dc.subjectgeneticsru_RU
dc.subjectgenome-wide association studyru_RU
dc.subjectsurvival analysisru_RU
dc.subjectconditional analysisru_RU
dc.subjectCYLDru_RU
dc.subjectNOD2ru_RU
dc.titleIdentification of a new locus at 16q12 associated with time to asthma onsetru_RU
dc.typeArticleru_RU
Располагается в коллекциях:Journal of Allergy and Clinical Immunology

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