title: Comparison of Parkinson risk in Ashkenazi Jewish patients with Gaucher disease and GBA heterozygotes.
abstract: OBJECTIVE
  Information on age-specific risk for Parkinson disease (PD) in patients with Gaucher disease (GD) and glucocerebrosidase (GBA) heterozygotes is important for understanding the pathophysiology of the genetic association and for counseling these populations.
  
  
  OBJECTIVE
  To estimate the age-specific risk for PD in Ashkenazi Jewish patients with type 1 GD and in GBA heterozygotes.
  
  
  METHODS
  The study included patients with GD from 2 tertiary centers, Shaare Zedek Medical Center, Jerusalem, Israel (n = 332) and Mount Sinai School of Medicine, New York, New York (n = 95). GBA noncarrier non-PD spouse control participants were recruited at the Center for Parkinson's Disease at Columbia University, New York (n = 77). All participants were Ashekanzi Jewish and most patients (98.1%) with GD carried at least 1 N370S mutation.
  
  
  METHODS
  The main outcome measure was a diagnosis of PD. Diagnosis was established in patients with GD on examination. We used a validated family history interview that identifies PD with a sensitivity of 95.5% and specificity of 96.2% to identify PD in family members. Kaplan-Meier survival curves were used to estimate age-specific PD risk among patients with GD (n = 427), among their parents who are obligate GBA mutation carriers (heterozygotes, n = 694), and among noncarriers (parents of non-PD, non-GD control participants, n = 154). The age-specific risk was compared among groups using the log-rank test.
  
  
  RESULTS
  Among those who developed PD, patients with GD had a younger age at onset than GBA heterozygotes (mean, 54.2 vs 65.2 years, respectively; P = .003). Estimated age-specific risk for PD at 60 and 80 years of age was 4.7% and 9.1% among patients with GD, 1.5% and 7.7% among heterozygotes, and 0.7% and 2.1% among noncarriers, respectively. The risk for PD was higher in patients with GD than noncarriers (P = .008, log-rank test) and in heterozygotes than noncarriers (P = .03, log-rank test), but it did not reach statistical significance between patients with GD and GBA heterozygotes (P = .07, log-rank test).
  
  
  CONCLUSIONS
  Patients with GD and GBA heterozygotes have an increased age-specific risk for PD compared with control individuals, with a similar magnitude of PD risk by 80 years of age; however, the number of mutant alleles may play an important role in age at PD onset.
authors.affiliation: The Taub Institute, Department of Neurology, Columbia University Medical Center, New York, New York.
authors.forename: Roy N
authors.initials: RN
authors.lastname: Alcalay
authors.affiliation: Gaucher Clinic, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Tama
authors.initials: T
authors.lastname: Dinur
authors.affiliation: The Taub Institute, Department of Neurology, Columbia University Medical Center, New York, New York.
authors.forename: Timothy
authors.initials: T
authors.lastname: Quinn
authors.affiliation: The Taub Institute, Department of Neurology, Columbia University Medical Center, New York, New York.
authors.forename: Karina
authors.initials: K
authors.lastname: Sakanaka
authors.affiliation: The Taub Institute, Department of Neurology, Columbia University Medical Center, New York, New York.
authors.forename: Oren
authors.initials: O
authors.lastname: Levy
authors.affiliation: The Taub Institute, Department of Neurology, Columbia University Medical Center, New York, New York.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Waters
authors.affiliation: The Taub Institute, Department of Neurology, Columbia University Medical Center, New York, New York.
authors.forename: Stanley
authors.initials: S
authors.lastname: Fahn
authors.affiliation: Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, New York.
authors.forename: Tsvyatko
authors.initials: T
authors.lastname: Dorovski
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, New York, New York5Department of Medicine, Columbia University Medical Center, New York, New York.
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Chung
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York, New York.
authors.forename: Michael
authors.initials: M
authors.lastname: Pauciulo
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio7Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: William
authors.initials: W
authors.lastname: Nichols
authors.affiliation: Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York.
authors.forename: Huma Q
authors.initials: HQ
authors.lastname: Rana
authors.affiliation: Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York.
authors.forename: Manisha
authors.initials: M
authors.lastname: Balwani
authors.affiliation: Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York.
authors.forename: Louise
authors.initials: L
authors.lastname: Bier
authors.affiliation: Gaucher Clinic, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Deborah
authors.initials: D
authors.lastname: Elstein
authors.affiliation: Gaucher Clinic, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Ari
authors.initials: A
authors.lastname: Zimran
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005776:Gaucher Disease / Q000150:complications / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005962:Glucosylceramidase / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007585:Jews / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000150:complications / Q000235:genetics*; D012306:Risk; D055815:Young Adult
chemical_list: D005962:Glucosylceramidase
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