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Novel genes and insights in complete asthma remission : a genome-wide association study on clinical and complete asthma remission

Vonk, J. M. and Nieuwenhuis, M. A. E. and Dijk, F. N. and Boudier, A. and Siroux, V. and Bouzigon, E. and Probst-Hensch, N. and Imboden, M. and Keidel, D. and Sin, D. and Bossé, Y. and Hao, K. and van den Berge, M. and Faiz, A. and Koppelman, G. H. and Postma, D. S.. (2018) Novel genes and insights in complete asthma remission : a genome-wide association study on clinical and complete asthma remission. Clinical & Experimental Allergy, 48 (10). pp. 1286-1296.

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Official URL: https://edoc.unibas.ch/65686/

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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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Chronic Disease Epidemiology > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch)
03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Probst-Hensch, Nicole and Imboden, Medea and Keidel, Dirk
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Wiley
ISSN:0954-7894
e-ISSN:1365-2222
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:15 Nov 2018 14:07
Deposited On:15 Nov 2018 14:07

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