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A cumulative genetic risk score predicts progression in P arkinson's disease
Author(s) -
Pihlstrøm Lasse,
Morset Kristina Rebekka,
Grimstad Espen,
Vitelli Valeria,
Toft Mathias
Publication year - 2016
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.26505
Subject(s) - disease , proportional hazards model , genetic association , medicine , oncology , genome wide association study , genetic model , genotype , biology , genetics , single nucleotide polymorphism , gene
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. © 2016 International Parkinson and Movement Disorder Society