title: Genetic susceptibility loci, environmental exposures, and Parkinson's disease: a case-control study of gene-environment interactions.
abstract: BACKGROUND
  Prior studies causally linked mutations in SNCA, MAPT, and LRRK2 genes with familial Parkinsonism. Genome-wide association studies have demonstrated association of single nucleotide polymorphisms (SNPs) in those three genes with sporadic Parkinson's disease (PD) susceptibility worldwide. Here we investigated the interactions between SNPs in those three susceptibility genes and environmental exposures (pesticides application, tobacco smoking, coffee drinking, and alcohol drinking) also associated with PD susceptibility.
  
  
  METHODS
  Pairwise interactions between environmental exposures and 18 variants (16 SNPs and two variable number tandem repeats, or "VNTRs") in SNCA, MAPT and LRRK2, were investigated using data from 1098 PD cases from the upper Midwest, USA and 1098 matched controls. Environmental exposures were assessed using a validated telephone interview script.
  
  
  RESULTS
  Five pairwise interactions had uncorrected P-values < 0.05. These included pairings of pesticides × SNCA rs3775423 or MAPT rs4792891, coffee drinking × MAPT H1/H2 haplotype or MAPT rs16940806, and alcohol drinking × MAPT rs2435211. None of these interactions remained significant after Bonferroni correction. Secondary analyses in strata defined by type of control (sibling or unrelated), sex, or age at onset of the case also did not identify significant interactions after Bonferroni correction.
  
  
  CONCLUSIONS
  This study documented limited pairwise interactions between established genetic and environmental risk factors for PD; however, the associations were not significant after correction for multiple testing.
authors.affiliation: Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Sun Ju
authors.initials: SJ
authors.lastname: Chung
authors.forename: Sebastian M
authors.initials: SM
authors.lastname: Armasu
authors.forename: Kari J
authors.initials: KJ
authors.lastname: Anderson
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Biernacka
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Lesnick
authors.forename: David N
authors.initials: DN
authors.lastname: Rider
authors.forename: Julie M
authors.initials: JM
authors.lastname: Cunningham
authors.forename: J Eric
authors.initials: JE
authors.lastname: Ahlskog
authors.forename: Roberta
authors.initials: R
authors.lastname: Frigerio
authors.forename: Demetrius M
authors.initials: DM
authors.lastname: Maraganore
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000209:etiology* / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012189:Retrospective Studies; D051844:alpha-Synuclein / Q000235:genetics; D016875:tau Proteins / Q000235:genetics
chemical_list: C054369:MAPT protein, human; C497604:SNCA protein, human; D051844:alpha-Synuclein; D016875:tau Proteins; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases