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

Xiang Zeng; Judith M Vonk; Diana A van der Plaat; Alen Faiz; Peter D Paré; Philippe Joubert; David Nickle; Corry-Anke Brandsma; Hans Kromhout; Roel Vermeulen; Xijin Xu; Xia Huo; Kim de Jong; H Marike Boezen

doi:10.1016/j.envint.2018.11.017

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

Xiang Zeng
, Judith M Vonk
, Diana A van der Plaat
, Alen Faiz
, Peter D Paré
, Philippe Joubert
, David Nickle
, Corry-Anke Brandsma
, Hans Kromhout
, Roel Vermeulen
, Xijin Xu
, Xia Huo
, Kim de Jong
, H Marike Boezen

University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands; Shantou University Medical College, Laboratory of Environmental Medicine and Developmental Toxicology, Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou, China; Xinxiang Medical University, School of Public Health, Department of Epidemiology and Health Statistics, Xinxiang, China.
University Medical Center Groningen
University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands; University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, the Netherlands.
University of British Columbia, Department of Medicine, Center for Heart Lung Innovation and Institute for Heart and Lung Health, St. Paul's Hospital, Vancouver, BC, Canada.
Institut universitaire de cardiologie et de pneumologie de Québec, Laval University, Québec, QC, Canada.
Merck & Co Inc, Rahway, NJ, USA.
Institute for Risk Assessment Sciences
Shantou University Medical College, Laboratory of Environmental Medicine and Developmental Toxicology, Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou, China.
Jinan University, School of Environment, Guangdong Key Laboratory of Environmental Pollution and Health, Guangzhou Key Laboratory of Environmental Exposure and Health, Guangzhou, China.
University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands. Electronic address: [email protected].

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Pages (from-to)	263-269
Number of pages	7
Journal	Environment international
Volume	122
DOIs	https://doi.org/10.1016/j.envint.2018.11.017
Publication status	Published - Jan 2019

Keywords

Genetics
Genome wide
Interaction
Occupational exposure
Respiratory symptoms

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1-s2.0-S0160412018312881-mainFinal published version, 286 KBLicence: CC BY-NC-ND

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title = "Genome-wide interaction study of gene-by-occupational exposures on respiratory symptoms",

abstract = "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.",

keywords = "Genetics, Genome wide, Interaction, Occupational exposure, Respiratory symptoms",

author = "Xiang Zeng and Vonk, \{Judith M\} and \{van der Plaat\}, \{Diana A\} and Alen Faiz and Par{\'e}, \{Peter D\} and Philippe Joubert and David Nickle and Corry-Anke Brandsma and Hans Kromhout and Roel Vermeulen and Xijin Xu and Xia Huo and \{de Jong\}, Kim and Boezen, \{H Marike\}",

year = "2019",

month = jan,

doi = "10.1016/j.envint.2018.11.017",

language = "English",

volume = "122",

pages = "263--269",

journal = "Environment international",

issn = "0160-4120",

publisher = "Elsevier Limited",

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T1 - Genome-wide interaction study of gene-by-occupational exposures on respiratory symptoms

AU - Zeng, Xiang

AU - Vonk, Judith M

AU - van der Plaat, Diana A

AU - Faiz, Alen

AU - Paré, Peter D

AU - Joubert, Philippe

AU - Nickle, David

AU - Brandsma, Corry-Anke

AU - Kromhout, Hans

AU - Vermeulen, Roel

AU - Xu, Xijin

AU - Huo, Xia

AU - de Jong, Kim

AU - Boezen, H Marike

PY - 2019/1

Y1 - 2019/1

N2 - 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.

AB - 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.

KW - Genetics

KW - Genome wide

KW - Interaction

KW - Occupational exposure

KW - Respiratory symptoms

U2 - 10.1016/j.envint.2018.11.017

DO - 10.1016/j.envint.2018.11.017

M3 - Article

C2 - 30449631

SN - 0160-4120

VL - 122

SP - 263

EP - 269

JO - Environment international

JF - Environment international

ER -

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

Abstract

Keywords

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