title: Genetic and Clinical Predictors of Deep Brain Stimulation in Young-Onset Parkinson's Disease.
abstract: OBJECTIVE
  In a cohort of patients with young-onset Parkinson's disease (PD), the authors assessed (1) the prevalence of genetic mutations in those who enrolled in deep brain stimulation (DBS) programs compared with those who did not enroll DBS programs and (2) specific genetic and clinical predictors of DBS enrollment.
  
  
  METHODS
  Subjects were participants from 3 sites (Columbia University, Rush University, and the University of Pennsylvania) in the Consortium on Risk for Early Onset Parkinson's Disease (CORE-PD) who had an age at onset < 51 years. The analyses presented here focus onglucocerebrosidase(GBA),leucine-rich repeat kinase 2(LRRK2), andparkin(PRKN) mutation carriers. Mutation carrier status, demographic data, and disease characteristics in individuals who did and did not enroll in DBS were analyzed. The association between mutation status and DBS placement was assessed in logistic regression models.
  
  
  RESULTS
  Patients who had PD with eitherGBA,LRRK2, orPRKNmutations were more common in the DBS group (n = 99) compared with the non-DBS group (n = 684; 26.5% vs. 16.8%, respectively;P= 0.02). In a multivariate logistic regression model,GBAmutation status (odds ratio, 2.1; 95% confidence interval, 1.0-4.3;P= 0.05) was associated with DBS surgery enrollment. However, when dyskinesia was included in the multivariate logistic regression model, dyskinesia had a strong association with DBS placement (odds ratio, 3.8; 95% confidence interval, 1.9-7.3;P< 0.0001), whereas the association between GBA mutation status and DBS placement did not persist (P= 0.25).
  
  
  CONCLUSIONS
  DBS populations are enriched with genetic mutation carriers. The effect of genetic mutation carriers on DBS outcomes warrants further exploration.
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Gian D
authors.initials: GD
authors.lastname: Pal
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Hall
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Bichun
authors.initials: B
authors.lastname: Ouyang
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Phelps
authors.affiliation: Department of Neurology and the Taub Institute, Columbia University Medical Center, New York, NY, USA.
authors.forename: Roy
authors.initials: R
authors.lastname: Alcalay
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center and the Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Pauciulo
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center and the Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Nichols
authors.affiliation: Department of Pathology and Cell Biology and the Taub Institute, Columbia University Medical Center, NY, New York, USA.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Clark
authors.affiliation: Department of Neurology and the Taub Institute, Columbia University Medical Center, New York, NY, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Mejia-Santana
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Lucia
authors.initials: L
authors.lastname: Blasucci
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Goetz
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Comella
authors.affiliation: PRKNson's Disease and Movement Disorders Center, Pennsylvania Hospital, Philadelphia, Pennsylvania, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Colcher
authors.affiliation: Department of Human Genetics, McGill University, Montreal, Quebec, Canada; Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Gan-Or
authors.affiliation: Department of Human Genetics, McGill University, Montreal, Quebec, Canada; Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; The Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rouleau
authors.affiliation: Department of Neurology and the Taub Institute, Columbia University Medical Center, New York, NY, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Marder
keywords: Parkinson's disease; deep brain stimulation (DBS); glucocerebrosidase (GBA); leucine-rich repeat kinase 2 (LRRK2); parkin (PRKN)