title: UCHL-1 is not a Parkinson's disease susceptibility gene.
abstract: OBJECTIVE
  The UCHL-1 gene is widely cited as a susceptibility factor for sporadic Parkinson's disease (PD). The strongest evidence comes from a meta-analysis of small studies that reported the S18Y polymorphism as protective against PD, after pooling studies of white and Asian subjects. Here, we present data that challenge this association.
  
  
  METHODS
  In a new large case-control study in white individuals (3,023 subjects), the S18Y variant was not protective against PD under any genetic model of inheritance. Similarly, a more powerful haplotype-tagging approach did not detect other associated variants.
  
  
  RESULTS
  Finally, in an updated S18Y-PD meta-analysis (6,594 subjects), no significant association was observed under additive, recessive, or dominant models (odds ratio = 1.00 [95% confidence interval: 0.74-1.33]; odds ratio = 1.01 [95% confidence interval: 0.76-1.35]; and odds ratio = 0.96 [95% confidence interval: 0.86-1.08], respectively), and a cumulative meta-analysis showed a trend toward a null effect.
  
  
  CONCLUSIONS
  Based on the current evidence, the UCHL-1 gene does not exhibit a protective effect in PD.
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, University College London, London, United Kingdom. danhealy@doctors.org.uk
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Healy
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Abou-Sleiman
authors.forename: Juan P
authors.initials: JP
authors.lastname: Casas
authors.forename: Kourosh R
authors.initials: KR
authors.lastname: Ahmadi
authors.forename: Timothy
authors.initials: T
authors.lastname: Lynch
authors.forename: Sonia
authors.initials: S
authors.lastname: Gandhi
authors.forename: Miratul M K
authors.initials: MM
authors.lastname: Muqit
authors.forename: Thomas
authors.initials: T
authors.lastname: Foltynie
authors.forename: Roger
authors.initials: R
authors.lastname: Barker
authors.forename: Kailash P
authors.initials: KP
authors.lastname: Bhatia
authors.forename: Niall P
authors.initials: NP
authors.lastname: Quinn
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lees
authors.forename: J Mark
authors.initials: JM
authors.lastname: Gibson
authors.forename: Janice L
authors.initials: JL
authors.lastname: Holton
authors.forename: Tamas
authors.initials: T
authors.lastname: Revesz
authors.forename: David B
authors.initials: DB
authors.lastname: Goldstein
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Wood
mesh_terms: D016022:Case-Control Studies; D016001:Confidence Intervals; D005260:Female; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D016017:Odds Ratio; D010300:Parkinson Disease / Q000235:genetics*; D011110:Polymorphism, Genetic; D012694:Serine / Q000235:genetics; D014443:Tyrosine / Q000235:genetics; D043222:Ubiquitin Thiolesterase / Q000235:genetics*
chemical_list: C482860:UCHL1 protein, human; D014443:Tyrosine; D012694:Serine; D043222:Ubiquitin Thiolesterase