Polygenic Risk Scores in a Prospective Parkinson's Disease Cohort

ABSTRACT 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