title: Genome-wide gene-environment interaction analysis of pesticide exposure and risk of Parkinson's disease.
abstract: Genetic factors and environmental exposures, including pesticides, contribute to the risk of Parkinson's disease (PD). There have been few studies of gene and pesticide exposure interactions in PD, and all of the prior studies used a candidate gene approach.
  
  
  
  We performed the first genome-wide gene-environment interaction analysis of pesticide exposure and risk of Parkinson's disease. Analyses were performed using data on >700,000 single nucleotide polymorphisms (SNPs) in 364 discordant sibling pairs. In addition to testing for SNP-pesticide interaction effects, we also performed exploratory analyses of gene-pesticide interactions at the gene level.
  
  
  
  None of the gene-environment interaction results were significant after genome-wide correction for multiple testing (α = 1.5E-07 for SNP-level tests; α = 2.1E-06 for gene-level tests). Top results in the SNP-level tests provided suggestive evidence (P < 5.0E-06) that the effect of pesticide exposure on PD risk may be modified by SNPs in the ERCC6L2 gene (P = 2.4E-06), which was also supported by suggestive evidence in the gene-level analysis (P = 4.7E-05). None of the candidate genes assessed in prior studies of gene-pesticide interactions reached statistical support in this genome-wide screen.
  
  
  
  Although no significant interactions were identified, several of the genes with suggestive evidence of gene-environment interaction effects have biological plausibility for PD risk. Further investigation of the role of those genes in PD risk, particularly in the context of pesticide exposure, in large and carefully recruited samples is warranted.
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Biernacka
authors.affiliation: Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Sun Ju
authors.initials: SJ
authors.lastname: Chung
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Sebastian M
authors.initials: SM
authors.lastname: Armasu
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Kari S
authors.initials: KS
authors.lastname: Anderson
authors.affiliation: Platform for Genome Analytics, Institutes of Neurogenetics & Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Lill
authors.affiliation: Platform for Genome Analytics, Institutes of Neurogenetics & Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany; School of Public Health, Faculty of Medicine, The Imperial College of Science, Technology, and Medicine, London, UK.
authors.forename: Lars
authors.initials: L
authors.lastname: Bertram
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Ahlskog
authors.affiliation: Department of Neurology, San Gerardo Hospital, Milan Center for Neuroscience, Monza, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Brighina
authors.affiliation: Department of Neurology, NorthShore University HealthSystem, Evanston, IL, USA.
authors.forename: Roberta
authors.initials: R
authors.lastname: Frigerio
authors.affiliation: Department of Neurology, NorthShore University HealthSystem, Evanston, IL, USA. Electronic address: dmaraganore@northshore.org.
authors.forename: Demetrius M
authors.initials: DM
authors.lastname: Maraganore
mesh_terms: D000368:Aged; D004265:DNA Helicases / Q000235:genetics; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000209:etiology* / Q000235:genetics*; D010575:Pesticides / Q000633:toxicity*; D012307:Risk Factors
chemical_list: D010575:Pesticides; D004265:DNA Helicases; C587425:ERCC6L2 protein, human
keywords: Gene-environment interaction; Genome wide association study; Parkinson's disease; Pesticide exposure