Polygenic Risk Scores in a Prospective Parkinson's Disease Cohort

Background: Ethnic-specific genetic risk assessment framework for Parkinson's disease (PD) is lacking for the Asian population. Objective: We investigated the association of a polygenic risk score (PRS) with PD incidence in a population-based Asian prospective cohort. Methods: Genetic, dietary, and lifestyle information were prospectively collected from 25,646 participants within the Singapore Chinese Health Study cohort. PRS was constructed with Asian-specific and top genome-wide association study variants. The association between PRS and PD incidence was evaluated with multivariable Cox proportional hazard models, Kaplan–Meier survival analysis, and concordance statistics. Results: A total of 333 incident cases were identified after a follow-up period of more than 20 years. Participants with PRS in the top tertile (hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.37–2.39) and middle tertile (HR, 1.35; 95% CI, 1.00–1.83) are at higher risk of developing PD after adjusting for dietary and lifestyle risk factors, with a shorter time to PD event in a Kaplan–Meier survival analysis (P < 0.001). Conclusion: We identified a PRS that was significantly associated with PD incidence in a prospective Chinese cohort after adjusting for dietary and lifestyle factors.