RESUMO
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.