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Novel genes and insights in complete asthma remission : a genome-wide association study on clinical and complete asthma remission
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 4486194
Author(s) Vonk, J. M.; Nieuwenhuis, M. A. E.; Dijk, F. N.; Boudier, A.; Siroux, V.; Bouzigon, E.; Probst-Hensch, N.; Imboden, M.; Keidel, D.; Sin, D.; Bossé, Y.; Hao, K.; van den Berge, M.; Faiz, A.; Koppelman, G. H.; Postma, D. S.
Author(s) at UniBasel Probst Hensch, Nicole
Imboden, Medea
Keidel, Dirk
Year 2018
Title Novel genes and insights in complete asthma remission : a genome-wide association study on clinical and complete asthma remission
Journal Clinical & Experimental Allergy
Volume 48
Number 10
Pages / Article-Number 1286-1296
Abstract Asthma is a chronic respiratory disease without a cure, although there exists spontaneous remission. Genome-wide association (GWA) studies have pinpointed genes associated with asthma development, but did not investigate asthma remission.; We performed a GWA study to develop insights in asthma remission.; Clinical remission (ClinR) was defined by the absence of asthma treatment and wheezing in the last year and asthma attacks in the last 3 years and complete remission (ComR) similarly but additionally with normal lung function and absence of bronchial hyperresponsiveness (BHR). A GWA study on both ClinR and ComR was performed in 790 asthmatics with initial doctor diagnosis of asthma and BHR and long-term follow-up. We assessed replication of the 25 top single nucleotide polymorphisms (SNPs) in 2 independent cohorts (total n = 456), followed by expression quantitative loci (eQTL) analyses of the 4 replicated SNPs in lung tissue and epithelium.; Of the 790 asthmatics, 178 (23%) had ClinR and 55 ComR (7%) after median follow-up of 15.5 (range 3.3-47.8) years. In ClinR, 1 of the 25 SNPs, rs2740102, replicated in a meta-analysis of the replication cohorts, which was an eQTL for POLI in lung tissue. In ComR, 3 SNPs replicated in a meta-analysis of the replication cohorts. The top-hit, rs6581895, almost reached genome-wide significance (P-value 4.68 × 10; -7; ) and was an eQTL for FRS2 and CCT in lung tissue. Rs1420101 was a cis-eQTL in lung tissue for IL1RL1 and IL18R1 and a trans-eQTL for IL13.; By defining a strict remission phenotype, we identified 3 SNPs to be associated with complete asthma remission, where 2 SNPs have plausible biological relevance in FRS2, CCT, IL1RL1, IL18R1 and IL13.
Publisher Wiley
ISSN/ISBN 0954-7894 ; 1365-2222
edoc-URL https://edoc.unibas.ch/65686/
Full Text on edoc No
Digital Object Identifier DOI 10.1111/cea.13181
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/29786918
ISI-Number WOS:000445725500005
Document type (ISI) Journal Article
 
   

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