Polygenic Risk Scores in a Prospective Parkinson's Disease Cohort

Mov Disord. 2021 Dec;36(12):2936-2940. doi: 10.1002/mds.28761. Epub 2021 Aug 17.


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. © 2021 International Parkinson and Movement Disorder Society.

Keywords: Parkinson's disease; neurogenetics; polygenic risk score; prospective cohort.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cohort Studies
  • Genome-Wide Association Study
  • Humans
  • Parkinson Disease* / complications
  • Parkinson Disease* / epidemiology
  • Parkinson Disease* / genetics
  • Prospective Studies
  • Risk Factors