Ming-Wei Sia1, Jia-Nee Foo2,3, Seyed-Ehsan Saffari4,5, Aidan Sheng-Yong Wong5, Chiea-Chuen Khor1,3, Jian-Min Yuan6, Eng-King Tan5, Woon-Puay Koh7, Louis Chew-Seng Tan1,5. 1. Duke-NUS Medical School, Singapore. 2. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore. 3. Department of Human Genetics, Genome Institute of Singapore, Singapore. 4. Health Services & Systems Research, Duke-NUS Medical School, Singapore. 5. Department of Neurology, National Neuroscience Institute, Singapore. 6. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. 7. Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
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 < 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.
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.
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