title: A cumulative genetic risk score predicts progression in Parkinson's disease.
abstract: BACKGROUND
  The contribution of genetic variability to clinical heterogeneity in Parkinson's disease is insufficiently understood. We aimed to investigate the effect of cumulative genetic risk on clinical outcomes.
  
  
  METHODS
  In a single-center study of 336 patients we genotyped 19 independent susceptibility variants identified in genome-wide association studies of Parkinson's disease. We tested for association between a cumulative genetic risk score and 3 outcome measures: survival, time until progression to Hoehn and Yahr stage 3, and Unified Parkinson's Disease Rating Scale motor score severity.
  
  
  RESULTS
  Genetic risk score was significantly associated with time from diagnosis to Hoehn and Yahr stage 3 in a Cox regression model (P = 0.010). We observed no clear association for the other outcomes.
  
  
  CONCLUSIONS
  We present results linking cumulative genetic risk to a motor outcome in Parkinson's disease. Our findings provide a valuable starting point for future large-scale efforts to map the genetic determinants of phenotypic variability.
authors: Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.|Department of Neurology, Oslo University Hospital, Oslo, Norway.
authors: Lasse
authors: L
authors: Pihlstrøm
authors: Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors: Kristina Rebekka
authors: KR
authors: Morset
authors: Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors: Espen
authors: E
authors: Grimstad
authors: Oslo Center for Biostatistics and Epidemiology, Department of Biostatistics, University of Oslo, Oslo, Norway.
authors: Valeria
authors: V
authors: Vitelli
authors: Department of Neurology, Oslo University Hospital, Oslo, Norway.
authors: Mathias
authors: M
authors: Toft
mesh_terms: D018450:Disease Progression; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D010300:Parkinson Disease / Q000235:genetics* / Q000503:physiopathology; D018570:Risk Assessment; D012720:Severity of Illness Index; D016019:Survival Analysis
keywords: GWAS; Hoehn and Yahr; Parkinson's disease; genetics; progression