Genome-wide interaction study of gene-by-occupational exposures on respiratory symptoms

Zeng, X; Vonk, JM; van der Plaat, DA; Faiz, A; Paré, PD; Joubert, P; Nickle, D; Brandsma, CA; Kromhout, H; Vermeulen, R; Xu, X; Huo, X; de Jong, K; Boezen, HM

Genome-wide interaction study of gene-by-occupational exposures on respiratory symptoms

Zeng, X Vonk, JM van der Plaat, DA Faiz, A

Paré, PD Joubert, P Nickle, D Brandsma, CA Kromhout, H Vermeulen, R Xu, X Huo, X de Jong, K Boezen, HM

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Publication Type:: Journal Article
Citation:: Environment International, 2019, 122 pp. 263 - 269
Issue Date:: 2019-01-01

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Field	Value	Language
dc.contributor.author	Zeng, X	en_US
dc.contributor.author	Vonk, JM	en_US
dc.contributor.author	van der Plaat, DA	en_US
dc.contributor.author	Faiz, A https://orcid.org/0000-0003-1740-3538	en_US
dc.contributor.author	Paré, PD	en_US
dc.contributor.author	Joubert, P	en_US
dc.contributor.author	Nickle, D	en_US
dc.contributor.author	Brandsma, CA	en_US
dc.contributor.author	Kromhout, H	en_US
dc.contributor.author	Vermeulen, R	en_US
dc.contributor.author	Xu, X	en_US
dc.contributor.author	Huo, X	en_US
dc.contributor.author	de Jong, K	en_US
dc.contributor.author	Boezen, HM	en_US
dc.date.available	2018-11-08	en_US
dc.date.issued	2019-01-01	en_US
dc.identifier.citation	Environment International, 2019, 122 pp. 263 - 269	en_US
dc.identifier.issn	0160-4120	en_US
dc.identifier.uri	http://hdl.handle.net/10453/135843
dc.description.abstract	© 2018 Elsevier Ltd Respiratory symptoms are important indicators of respiratory diseases. Both genetic and environmental factors contribute to respiratory symptoms development but less is known about gene-environment interactions. We aimed to assess interactions between single nucleotide polymorphisms (SNPs) and occupational exposures on respiratory symptoms cough, dyspnea and phlegm. As identification cohort LifeLines I (n = 7976 subjects) was used. Job-specific exposure was estimated using the ALOHA + job exposure matrix. SNP-by-occupational exposure interactions on respiratory symptoms were tested using logistic regression adjusted for gender, age, and current smoking. SNP-by-exposure interactions with a p-value <10 −4 were tested for replication in two independent cohorts: LifeLines II (n = 5260) and the Vlagtwedde-Vlaardingen cohort (n = 1529). The interaction estimates of the replication cohorts were meta-analyzed using PLINK. Replication was achieved when the meta-analysis p-value was <0.05 and the interaction effect had the same direction as in the identification cohort. Additionally, we assessed whether replicated SNPs associated with gene expression by analyzing if they were cis-acting expression quantitative trait loci (eQTL) in lung tissue. In the replication meta-analysis, sixteen out of 477 identified SNP-by-occupational exposure interactions had a p-value <0.05 and 9 of these interactions had the same direction as in the identification cohort. Several identified loci were plausible candidates for respiratory symptoms, such as TMPRSS9, SERPINH1, TOX3, and ARHGAP18. Three replicated SNPs were cis-eQTLs for FCER1A, CHN1, and TIMM13 in lung tissue. Taken together, this genome-wide SNP-by-occupational exposure interaction study in relation to cough, dyspnea, and phlegm identified several suggestive susceptibility genes. Further research should determine if these genes are true susceptibility loci for respiratory symptoms in relation to occupational exposures.	en_US
dc.relation.ispartof	Environment International	en_US
dc.relation.isbasedon	10.1016/j.envint.2018.11.017	en_US
dc.subject.classification	Environmental Sciences	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Respiratory Tract Diseases	en_US
dc.subject.mesh	Cohort Studies	en_US
dc.subject.mesh	Occupational Exposure	en_US
dc.subject.mesh	Polymorphism, Single Nucleotide	en_US
dc.subject.mesh	Genome-Wide Association Study	en_US
dc.title	Genome-wide interaction study of gene-by-occupational exposures on respiratory symptoms	en_US
dc.type	Journal Article
utslib.citation.volume	122	en_US
utslib.for	0604 Genetics	en_US
utslib.for	1102 Cardiorespiratory Medicine and Haematology	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	open_access
pubs.publication-status	Published	en_US
pubs.volume	122	en_US

Abstract:

© 2018 Elsevier Ltd Respiratory symptoms are important indicators of respiratory diseases. Both genetic and environmental factors contribute to respiratory symptoms development but less is known about gene-environment interactions. We aimed to assess interactions between single nucleotide polymorphisms (SNPs) and occupational exposures on respiratory symptoms cough, dyspnea and phlegm. As identification cohort LifeLines I (n = 7976 subjects) was used. Job-specific exposure was estimated using the ALOHA + job exposure matrix. SNP-by-occupational exposure interactions on respiratory symptoms were tested using logistic regression adjusted for gender, age, and current smoking. SNP-by-exposure interactions with a p-value <10 −4 were tested for replication in two independent cohorts: LifeLines II (n = 5260) and the Vlagtwedde-Vlaardingen cohort (n = 1529). The interaction estimates of the replication cohorts were meta-analyzed using PLINK. Replication was achieved when the meta-analysis p-value was <0.05 and the interaction effect had the same direction as in the identification cohort. Additionally, we assessed whether replicated SNPs associated with gene expression by analyzing if they were cis-acting expression quantitative trait loci (eQTL) in lung tissue. In the replication meta-analysis, sixteen out of 477 identified SNP-by-occupational exposure interactions had a p-value <0.05 and 9 of these interactions had the same direction as in the identification cohort. Several identified loci were plausible candidates for respiratory symptoms, such as TMPRSS9, SERPINH1, TOX3, and ARHGAP18. Three replicated SNPs were cis-eQTLs for FCER1A, CHN1, and TIMM13 in lung tissue. Taken together, this genome-wide SNP-by-occupational exposure interaction study in relation to cough, dyspnea, and phlegm identified several suggestive susceptibility genes. Further research should determine if these genes are true susceptibility loci for respiratory symptoms in relation to occupational exposures.

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http://hdl.handle.net/10453/135843