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

Abstract : 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 (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. 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 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. Conclusions and clinical relevance: 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.
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https://www.hal.inserm.fr/inserm-03156815
Contributor : Valérie Siroux <>
Submitted on : Tuesday, March 2, 2021 - 4:58:48 PM
Last modification on : Tuesday, May 11, 2021 - 11:36:39 AM
Long-term archiving on: : Monday, May 31, 2021 - 7:36:41 PM

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J. Vonk, M. Nieuwenhuis, F. Dijk, A. Boudier, V. Siroux, et al.. Novel genes and insights in complete asthma remission: A genome-wide association study on clinical and complete asthma remission. Clinical & Experimental Allergy, 2018, 48 (10), pp.1286-1296. ⟨10.1111/cea.13181⟩. ⟨inserm-03156815⟩

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