title: Glucocerebrosidase gene mutations: a risk factor for Lewy body disorders.
abstract: BACKGROUND
  Mutations in the glucocerebrosidase (GBA) gene have been reported to modify risk for Parkinson disease (PD) and dementia with Lewy bodies (DLB). However, these findings have not been consistently replicated, and most studies have had substantial methodological shortcomings.
  
  
  OBJECTIVE
  To better assess the role of GBA variants in altering risk for Lewy body disorders.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  Four movement disorder clinics in the Seattle, Washington, area.
  
  
  METHODS
  Seven hundred twenty-one patients with PD, 554 healthy control subjects, and 57 patients with DLB.
  
  
  METHODS
  Disease status and presence or absence of the 2 most common GBA mutations (N370S and L444P).
  
  
  RESULTS
  We observed a significantly higher heterozygote frequency for the 2 mutations in patients with PD (2.9%; P <.001) and those with DLB (3.5%; P = .045) compared with control subjects (0.4%).
  
  
  CONCLUSIONS
  Our findings suggest that GBA mutations exert a large effect on susceptibility for Lewy body disorders at the individual level but are associated with a modest (approximately 3%) population-attributable risk in individuals of European ancestry.
authors.affiliation: Department of Neurology, University of Washington School of Medicine, Seattle, USA.
authors.forename: Ignacio F
authors.initials: IF
authors.lastname: Mata
authors.forename: Ali
authors.initials: A
authors.lastname: Samii
authors.forename: Seth H
authors.initials: SH
authors.lastname: Schneer
authors.forename: John W
authors.initials: JW
authors.lastname: Roberts
authors.forename: Alida
authors.initials: A
authors.lastname: Griffith
authors.forename: Berta C
authors.initials: BC
authors.lastname: Leis
authors.forename: Gerard D
authors.initials: GD
authors.lastname: Schellenberg
authors.forename: Ellen
authors.initials: E
authors.lastname: Sidransky
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Bird
authors.forename: James B
authors.initials: JB
authors.lastname: Leverenz
authors.forename: Debby
authors.initials: D
authors.lastname: Tsuang
authors.forename: Cyrus P
authors.initials: CP
authors.lastname: Zabetian
mesh_terms: D000368:Aged; D001216:Asparagine / Q000235:genetics; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D007930:Leucine / Q000235:genetics; D020961:Lewy Body Disease / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics; D011392:Proline / Q000235:genetics; D012307:Risk Factors; D012694:Serine / Q000235:genetics
chemical_list: D012694:Serine; D001216:Asparagine; D011392:Proline; D005962:Glucosylceramidase; D007930:Leucine