title: Genome-wide interaction study of gene-by-occupational exposure and effects on FEV1 levels.
abstract: BACKGROUND
  Chronic obstructive pulmonary disease (COPD) is a complex disease characterized by impaired lung function and airway obstruction resulting from interactions between multiple genes and multiple environmental exposures. Thus far, genome-wide association studies have largely disregarded environmental factors that might trigger the development of lung function impairment and COPD, such as occupational exposures, which are thought to contribute to 15% to 20% of the COPD prevalence.
  
  
  OBJECTIVE
  We performed a genome-wide interaction study to identify novel susceptibility loci for occupational exposure to biological dust, mineral dust, and gases and fumes in relation to FEV1 levels.
  
  
  METHODS
  We performed an identification analysis in 12,400 subjects from the LifeLines cohort study and verified our findings in 1436 subjects from a second independent cohort, the Vlagtwedde-Vlaardingen cohort. Additionally, we assessed whether replicated single nucleotide polymorphisms (SNPs) were cis-acting expression (mRNA) quantitative trait loci in lung tissue.
  
  
  RESULTS
  Of the 7 replicated SNPs that interacted with one of the occupational exposures, several identified loci were plausible candidates that might be involved in biological pathways leading to lung function impairment, such as PCDH9 and GALNT13. Two of the 7 replicated SNPs were cis-acting expression quantitative trait loci associated with gene expression of PDE4D and TMEM176A in lung tissue.
  
  
  CONCLUSIONS
  This genome-wide interaction study on occupational exposures in relation to the level of lung function identified several novel genes. Further research should determine whether the identified genes are true susceptibility loci for occupational exposures and whether these SNP-by-exposure interactions consequently contribute to the development of COPD.
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Kim
authors.initials: K
authors.lastname: de Jong
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Judith M
authors.initials: JM
authors.lastname: Vonk
authors.affiliation: Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Timens
authors.affiliation: Institut universitaire de cardiologie et de pneumologie de Québec, Department of Molecular Medicine, Laval University, Quebec City, Quebec, Canada.
authors.forename: Yohan
authors.initials: Y
authors.lastname: Bossé
authors.affiliation: Department of Medicine and Center for Heart Lung Innovation, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Don D
authors.initials: DD
authors.lastname: Sin
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Ke
authors.initials: K
authors.lastname: Hao
authors.affiliation: Division of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), University of Utrecht, Utrecht, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Kromhout
authors.affiliation: Division of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), University of Utrecht, Utrecht, The Netherlands.
authors.forename: Roel
authors.initials: R
authors.lastname: Vermeulen
authors.affiliation: Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: h.m.boezen@umcg.nl.
authors.forename: H Marike
authors.initials: HM
authors.lastname: Boezen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000395:Air Pollutants, Occupational / Q000633:toxicity*; D015331:Cohort Studies; D004391:Dust; D005260:Female; D005541:Forced Expiratory Volume; D005740:Gases / Q000633:toxicity*; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D016273:Occupational Exposure / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012333:RNA, Messenger / Q000378:metabolism; D055815:Young Adult
chemical_list: D000395:Air Pollutants, Occupational; D004391:Dust; D005740:Gases; D012333:RNA, Messenger
keywords: Genetics; gene expression; interactions; lung function; occupational exposures