title: A multicenter study of glucocerebrosidase mutations in dementia with Lewy bodies.
abstract: OBJECTIVE
  While mutations in glucocerebrosidase (GBA1) are associated with an increased risk for Parkinson disease (PD), it is important to establish whether such mutations are also a common risk factor for other Lewy body disorders.
  
  
  OBJECTIVE
  To establish whether GBA1 mutations are a risk factor for dementia with Lewy bodies (DLB). DESIGN We compared genotype data on patients and controls from 11 centers. Data concerning demographics, age at onset, disease duration, and clinical and pathological features were collected when available. We conducted pooled analyses using logistic regression to investigate GBA1 mutation carrier status as predicting DLB or PD with dementia status, using common control subjects as a reference group. Random-effects meta-analyses were conducted to account for additional heterogeneity.
  
  
  METHODS
  Eleven centers from sites around the world performing genotyping.
  
  
  METHODS
  Seven hundred twenty-one cases met diagnostic criteria for DLB and 151 had PD with dementia. We compared these cases with 1962 controls from the same centers matched for age, sex, and ethnicity.
  
  
  METHODS
  Frequency of GBA1 mutations in cases and controls. RESULTS We found a significant association between GBA1 mutation carrier status and DLB, with an odds ratio of 8.28 (95% CI, 4.78-14.88). The odds ratio for PD with dementia was 6.48 (95% CI, 2.53-15.37). The mean age at diagnosis of DLB was earlier in GBA1 mutation carriers than in noncarriers (63.5 vs 68.9 years; P < .001), with higher disease severity scores.
  
  
  CONCLUSIONS
  Mutations in GBA1 are a significant risk factor for DLB. GBA1 mutations likely play an even larger role in the genetic etiology of DLB than in PD, providing insight into the role of glucocerebrosidase in Lewy body disease.
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
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authors.lastname: Halliday
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authors.forename: Claudia
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authors.lastname: Landazabal
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mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D005838:Genotype; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D020961:Lewy Body Disease / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D012307:Risk Factors
chemical_list: D005962:Glucosylceramidase