A cumulative genetic risk score predicts progression in Parkinson's disease

Mov Disord. 2016 Apr;31(4):487-90. doi: 10.1002/mds.26505. Epub 2016 Feb 8.


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.

Keywords: GWAS; Hoehn and Yahr; Parkinson's disease; genetics; progression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Disease Progression*
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study
  • Humans
  • Parkinson Disease / genetics*
  • Parkinson Disease / physiopathology
  • Risk Assessment
  • Severity of Illness Index*
  • Survival Analysis