Approved Research

Studying common genetic risk burden for epilepsy in Parkinson's disease patients of European and Latin American origin

Universidad del Desarrollo

Lay summary

Parkinson's disease is a chronic disabling neurodegenerative disease that affects 2-3% of people over 65 years old and is characterized by multiple motor and non-motor features. Parkinson's disease patients have double the risk of developing epilepsy than the general population. Epilepsy is characterized by recurrent and unprovoked seizures and in 66% of cases can be pharmacologically controlled. Thus, early identification of individuals at risk may improve patient management. Both Parkinson's disease and epilepsy have a strong genetic component. Yet, the epilepsy genetic risk carried by Parkinson's disease patients and how it relates to seizures or other Parkinson's disease features has not been evaluated yet. Currently, it's possible to measure the cumulative risk given by thousands of common genetic variants in a single individual with polygenic risk scores (PRS). PRS can identify individuals at high risk of developing disease, identify individuals with particular disease features, or be combined with other biomarkers for patient stratification. Future precision medicine applications of PRS will benefit patients. These include earlier interventions, accurate diagnoses, and adequate drug treatment. However, as most PRS were developed using populations of European origin, they do not perform well in non-European populations. Considering that Parkinson's disease incidence in Latin American populations is among the highest, the implementation of methods that can integrate Latin American individuals into PRS calculations will accelerate future precision medicine applications in currently underrepresented populations. Here, under the hypothesis that: "Parkinson's disease patients presenting seizures of European and Latin American origin have a higher common genetic risk burden towards epilepsy" we propose to study epilepsy-PRS in Parkinson's disease patients from the UK biobank and implement methods to study epilepsy-PRS in Latin American individuals within a period of three years.

Aims:

1) To evaluate common genetic risk burden towards epilepsy with PRS in Parkinson disease patients.

2) To integrate Latin American epilepsy cases and controls to epilepsy-PRS calculations using local-ancestry based methods and evaluate performance.

3) To evaluate local-ancestry based epilepsy-PRS in Latin American Parkinson's disease patients.

Our project will evaluate how the common genetic risk burden for epilepsy carried by Parkinson's disease patients contributes to disease presentation and heterogeneity. We will aid in the early identification and intervention of patients at risk of seizures. We will implement a framework for the integration of Latin American individuals into this analysis and train local scientist in the study of large-scale biobank data. The resulting infrastructure will enable the study of multiple additional hypothesis.