title: SNCA, MAPT, and GSK3B in Parkinson disease: a gene-gene interaction study.
abstract: OBJECTIVE
  Recent evidence suggests that variation in the SNCA, MAPT, and GSK3B genes interacts in affecting risk for Parkinson disease (PD). In the current study, we attempt to validate previously published findings, evaluating gene-gene interactions between SNCA, MAPT, and GSK3B in association with PD.
  
  
  METHODS
  Three Caucasian PD patient-control series from the United States, Ireland, and Norway (combined n = 1020 patients and 1095 controls) were genotyped for SNCA rs356219, MAPT H1/H2-discriminating SNP rs1052553, and GSK3B rs334558 and rs6438552.
  
  
  RESULTS
  Our findings indicate that as previously reported, the SNCA rs356219-G allele and MAPT rs1052553 (H1 haplotype) were both associated with an increased risk of PD, whilst contrary to previous reports, GSK3B variants were not. No pair-wise interaction was observed between SNCA, MAPT, and GSK3B; the risk effects of SNCA rs356219-G and MAPT rs1052553-H1 were seen in a similar manner across genotypes of other variants, with no evidence suggesting synergistic, antagonistic, or deferential effects.
  
  
  CONCLUSIONS
  In the Caucasian patient-control series examined, risk for PD was influenced by variation in SNCA and MAPT but not GSK3B. Additionally, those three genes did not interact in determining disease risk.
authors.affiliation: Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA. christian.wider@chuv.ch
authors.forename: C
authors.initials: C
authors.lastname: Wider
authors.forename: C
authors.initials: C
authors.lastname: Vilariño-Güell
authors.forename: M G
authors.initials: MG
authors.lastname: Heckman
authors.forename: B
authors.initials: B
authors.lastname: Jasinska-Myga
authors.forename: A I
authors.initials: AI
authors.lastname: Ortolaza-Soto
authors.forename: N N
authors.initials: NN
authors.lastname: Diehl
authors.forename: J E
authors.initials: JE
authors.lastname: Crook
authors.forename: S A
authors.initials: SA
authors.lastname: Cobb
authors.forename: J A
authors.initials: JA
authors.lastname: Bacon
authors.forename: J O
authors.initials: JO
authors.lastname: Aasly
authors.forename: J M
authors.initials: JM
authors.lastname: Gibson
authors.forename: T
authors.initials: T
authors.lastname: Lynch
authors.forename: R J
authors.initials: RJ
authors.lastname: Uitti
authors.forename: Z K
authors.initials: ZK
authors.lastname: Wszolek
authors.forename: M J
authors.initials: MJ
authors.lastname: Farrer
authors.forename: O A
authors.initials: OA
authors.lastname: Ross
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004843:Epistasis, Genetic / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies; D018570:Risk Assessment / Q000379:methods; D055815:Young Adult; D051844:alpha-Synuclein / Q000235:genetics*; D016875:tau Proteins / Q000235:genetics*
chemical_list: C497604:SNCA protein, human; D051844:alpha-Synuclein; D016875:tau Proteins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3