Volume 36, Issue 12 p. 2936-2940
Brief Report

Polygenic Risk Scores in a Prospective Parkinson's Disease Cohort

Ming-Wei Sia B.Eng. (Hons)

Ming-Wei Sia B.Eng. (Hons)

Duke-NUS Medical School, Singapore

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Jia-Nee Foo PhD

Jia-Nee Foo PhD

Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore

Department of Human Genetics, Genome Institute of Singapore, Singapore

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Seyed-Ehsan Saffari PhD

Seyed-Ehsan Saffari PhD

Health Services & Systems Research, Duke-NUS Medical School, Singapore

Department of Neurology, National Neuroscience Institute, Singapore

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Aidan Sheng-Yong Wong Dip PharmSci

Aidan Sheng-Yong Wong Dip PharmSci

Department of Neurology, National Neuroscience Institute, Singapore

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Chiea-Chuen Khor MBBS, PhD

Chiea-Chuen Khor MBBS, PhD

Duke-NUS Medical School, Singapore

Department of Human Genetics, Genome Institute of Singapore, Singapore

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Jian-Min Yuan MD, PhD

Jian-Min Yuan MD, PhD

Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

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Eng-King Tan MBBS, MRCP, FAMS, FRCP

Eng-King Tan MBBS, MRCP, FAMS, FRCP

Department of Neurology, National Neuroscience Institute, Singapore

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Woon-Puay Koh MBBS (Hons), PhD

Woon-Puay Koh MBBS (Hons), PhD

Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

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Louis Chew-Seng Tan MBBS, MRCP, FAMS, FRCP

Corresponding Author

Louis Chew-Seng Tan MBBS, MRCP, FAMS, FRCP

Duke-NUS Medical School, Singapore

Department of Neurology, National Neuroscience Institute, Singapore

*Correspondence to: Dr. Louis Chew-Seng Tan, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore; E-mail: [email protected]

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First published: 17 August 2021
Citations: 2

Relevant conflicts of interest/financial disclosures: Nothing to report.

Funding agencies: The Singapore Chinese Health Study was supported by grants from the National Medical Research Council, Singapore (NMRC/CIRG/1456/2016), and the National Institutes of Health (R01 CA144034 and UM1 CA182876). Additional support was received from the Singapore Ministry of Health's National Medical Research Council under its Translational and Clinical Research Flagship Programme (NMRC/TCR/013-NNI/2014), Open Fund Large Collaborative Grant (MOH-OFLCG18May-0002), and National Research Foundation Singapore NRF-NRFF2016-03.

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. © 2021 International Parkinson and Movement Disorder Society

Data Availability Statement

Access to deidentified summary data may be requested, subject to material transfer agreements, from the corresponding author.