Polygenic load: Earlier disease onset but similar longitudinal progression in Parkinson's disease

ABSTRACT Objectives: In order to evaluate the influence of the genetic load of 49 genetic variants known to be associated with PD on the age at onset as well as on clinical outcome parameters. Background: PD patients show a large variability in phenotype and progression reflecting interindividual heterogeneity. This might be influenced by a diverse genetic architecture. Methods: Six hundred seventeen PD patients were included in this study and stratified by their “genetic load,” which is based on the weighted odds ratios of 49 genetic variants known to be associated with PD from genome‐wide association studies. Clinical parameters (H & Y, UPDRS‐III, MMSE, and Beck's Depression Inventory) were evaluated cross‐sectionally and in a subgroup longitudinally over 8 years. Results: PD patients with the highest genetic load were younger at disease onset, whereas severity of clinical parameters were similar compared to patients with the lowest genetic load. These findings could be confirmed regarding progression to clinical endpoints in the longitudinal analysis. Conclusion: A high genetic load is associated with a younger age at onset, which, in turn, might possibly promote more effective compensatory mechanisms resulting in a similar rate of disease progression. © 2018 International Parkinson and Movement Disorder Society