
SummaryBackgroundAsthma 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.ObjectiveWe performed a GWA study to develop insights in asthma remission.MethodsClinical 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.ResultsOf 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 RelevanceBy 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.
Male, MESH: Asthma, CHILDHOOD, MESH: Respiratory Function Tests, [SDV.GEN] Life Sciences [q-bio]/Genetics, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, DISEASE, RESPONSIVENESS, MESH: Genotype, MESH: Respiratory Mucosa, MESH: Genetic Association Studies, ADENOSINE 5'-MONOPHOSPHATE, MESH: Middle Aged, MESH: Genetic Predisposition to Disease, MESH: Patient Outcome Assessment, Single Nucleotide, Middle Aged, MESH: Gene Expression Regulation, Respiratory Function Tests, Phenotype, Female, Bronchial Hyperreactivity, MESH: Computational Biology, Adult, Genotype, Quantitative Trait Loci, 610, SPUTUM EOSINOPHILS, PHENOTYPES, MESH: Molecular Sequence Annotation, MESH: Phenotype, Polymorphism, Single Nucleotide, Humans, Genetic Predisposition to Disease, MESH: Polymorphism, Alleles, Genetic Association Studies, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, MESH: Alleles, MESH: Bronchial Hyperreactivity, Computational Biology, MESH: Adult, Molecular Sequence Annotation, ADULTS, MESH: Quantitative Trait Loci, MESH: Male, Asthma, Patient Outcome Assessment, Gene Expression Regulation, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Genome-Wide Association Study, RISK-FACTORS, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, FOLLOW-UP, MESH: Female, IL1RL1, Genome-Wide Association Study
Male, MESH: Asthma, CHILDHOOD, MESH: Respiratory Function Tests, [SDV.GEN] Life Sciences [q-bio]/Genetics, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, DISEASE, RESPONSIVENESS, MESH: Genotype, MESH: Respiratory Mucosa, MESH: Genetic Association Studies, ADENOSINE 5'-MONOPHOSPHATE, MESH: Middle Aged, MESH: Genetic Predisposition to Disease, MESH: Patient Outcome Assessment, Single Nucleotide, Middle Aged, MESH: Gene Expression Regulation, Respiratory Function Tests, Phenotype, Female, Bronchial Hyperreactivity, MESH: Computational Biology, Adult, Genotype, Quantitative Trait Loci, 610, SPUTUM EOSINOPHILS, PHENOTYPES, MESH: Molecular Sequence Annotation, MESH: Phenotype, Polymorphism, Single Nucleotide, Humans, Genetic Predisposition to Disease, MESH: Polymorphism, Alleles, Genetic Association Studies, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, MESH: Alleles, MESH: Bronchial Hyperreactivity, Computational Biology, MESH: Adult, Molecular Sequence Annotation, ADULTS, MESH: Quantitative Trait Loci, MESH: Male, Asthma, Patient Outcome Assessment, Gene Expression Regulation, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Genome-Wide Association Study, RISK-FACTORS, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, FOLLOW-UP, MESH: Female, IL1RL1, Genome-Wide Association Study
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