Novel genes and insights in complete asthma remission: A genome-wide association study on clinical and complete asthma remission
Vonk, JM
Nieuwenhuis, MAE
Dijk, FN
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, GH
Postma, DS
- Publication Type:
- Journal Article
- Citation:
- Clinical and Experimental Allergy, 2018, 48 (10), pp. 1286 - 1296
- Issue Date:
- 2018-10-01
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Vonk_et_al-2018-Clinical_&_Experimental_Allergy.pdf | Published Version | 747.53 kB | Adobe PDF |
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Vonk, JM | en_US |
dc.contributor.author | Nieuwenhuis, MAE | en_US |
dc.contributor.author | Dijk, FN | en_US |
dc.contributor.author | Boudier, A | en_US |
dc.contributor.author | Siroux, V | en_US |
dc.contributor.author | Bouzigon, E | en_US |
dc.contributor.author | Probst-Hensch, N | en_US |
dc.contributor.author | Imboden, M | en_US |
dc.contributor.author | Keidel, D | en_US |
dc.contributor.author | Sin, D | en_US |
dc.contributor.author | Bossé, Y | en_US |
dc.contributor.author | Hao, K | en_US |
dc.contributor.author | van den Berge, M | en_US |
dc.contributor.author |
Faiz, A https://orcid.org/0000-0003-1740-3538 |
en_US |
dc.contributor.author | Koppelman, GH | en_US |
dc.contributor.author | Postma, DS | en_US |
dc.date.available | 2018-03-29 | en_US |
dc.date.issued | 2018-10-01 | en_US |
dc.identifier.citation | Clinical and Experimental Allergy, 2018, 48 (10), pp. 1286 - 1296 | en_US |
dc.identifier.issn | 0954-7894 | en_US |
dc.identifier.uri | http://hdl.handle.net/10453/130674 | |
dc.description.abstract | © 2018 John Wiley & Sons Ltd 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. | en_US |
dc.relation.ispartof | Clinical and Experimental Allergy | en_US |
dc.relation.isbasedon | 10.1111/cea.13181 | en_US |
dc.subject.classification | Allergy | en_US |
dc.subject.mesh | Respiratory Mucosa | en_US |
dc.subject.mesh | Humans | en_US |
dc.subject.mesh | Asthma | en_US |
dc.subject.mesh | Bronchial Hyperreactivity | en_US |
dc.subject.mesh | Genetic Predisposition to Disease | en_US |
dc.subject.mesh | Respiratory Function Tests | en_US |
dc.subject.mesh | Computational Biology | en_US |
dc.subject.mesh | Gene Expression Regulation | en_US |
dc.subject.mesh | Genotype | en_US |
dc.subject.mesh | Phenotype | en_US |
dc.subject.mesh | Polymorphism, Single Nucleotide | en_US |
dc.subject.mesh | Alleles | en_US |
dc.subject.mesh | Quantitative Trait Loci | en_US |
dc.subject.mesh | Adult | en_US |
dc.subject.mesh | Middle Aged | en_US |
dc.subject.mesh | Female | en_US |
dc.subject.mesh | Male | en_US |
dc.subject.mesh | Genome-Wide Association Study | en_US |
dc.subject.mesh | Genetic Association Studies | en_US |
dc.subject.mesh | Molecular Sequence Annotation | en_US |
dc.subject.mesh | Patient Outcome Assessment | en_US |
dc.title | Novel genes and insights in complete asthma remission: A genome-wide association study on clinical and complete asthma remission | en_US |
dc.type | Journal Article | |
utslib.citation.volume | 10 | en_US |
utslib.citation.volume | 48 | en_US |
utslib.for | 1107 Immunology | en_US |
utslib.for | 1117 Public Health and Health Services | en_US |
utslib.for | 1111 Nutrition and Dietetics | en_US |
pubs.embargo.period | Not known | en_US |
pubs.organisational-group | /University of Technology Sydney | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science/School of Life Sciences | |
utslib.copyright.status | closed_access | |
pubs.issue | 10 | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 48 | en_US |
Abstract:
© 2018 John Wiley & Sons Ltd 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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