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Novel genes and insights in complete asthma remission: A genome‐wide association study on clinical and complete asthma remission
Author(s) -
Vonk J. M.,
Nieuwenhuis M. A. E.,
Dijk F. N.,
Boudier A.,
Siroux V.,
Bouzigon E.,
ProbstHensch N.,
Imboden M.,
Keidel D.,
Sin D.,
Bossé Y.,
Hao K.,
Berge M.,
Faiz A.,
Koppelman G. H.,
Postma D. S.
Publication year - 2018
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.13181
Subject(s) - asthma , single nucleotide polymorphism , genome wide association study , medicine , expression quantitative trait loci , bronchial hyperresponsiveness , immunology , respiratory disease , lung , gene , biology , genetics , genotype
Summary Background 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. Objective We performed a GWA study to develop insights in asthma remission. Methods 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 ( SNP s) in 2 independent cohorts (total n = 456), followed by expression quantitative loci ( eQTL ) analyses of the 4 replicated SNP s in lung tissue and epithelium. Results 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 SNP s, rs2740102, replicated in a meta‐analysis of the replication cohorts, which was an eQTL for POLI in lung tissue. In ComR, 3 SNP s 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 FRS 2 and CCT in lung tissue. Rs1420101 was a cis‐ eQTL in lung tissue for IL 1 RL 1 and IL 18R1 and a trans‐ eQTL for IL13 . Conclusions and Clinical Relevance By defining a strict remission phenotype, we identified 3 SNP s to be associated with complete asthma remission, where 2 SNP s have plausible biological relevance in FRS 2 , CCT , IL 1 RL 1, IL 18R1 and IL 13 .