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Parkinson's Disease GWAS-linked Park16 Carriers Show Greater Motor Progression: A Longitudinal Study Over 9 Years

16 Pages Posted: 20 Sep 2018

See all articles by Xiao Deng

Xiao Deng

Singapore General Hospital - Department of Neurology

Bin Xiao

Singapore General Hospital - Department of Neurology

John Carson Allen Jr

Duke-NUS Graduate Medical School Singapore

Yu-Lin Ng

Singapore General Hospital - Department of Neurology

Jia-Nee Foo

Agency for Science, Technology and Research (A*STAR) - Genome Institute of Singapore

Yew-Long Lo

Singapore General Hospital - Department of Neurology

Louis C. S. Tan

Singapore General Hospital - Department of Neurology; National Neuroscience Institute - Department of Neurology

Eng-King Tan

Singapore General Hospital - Department of Neurology; Duke-NUS Graduate Medical School Singapore

More...

Abstract

Background: Data on the long-term motor outcomes of GWAS-linked Parkinson disease (PD) carriers will be useful for clinical management.  

Methods: Over a 9-year period, carriers of PARK16 rs11240572 variant and non-carriers were followed up and evaluated using the modified Hoehn and Yahr (H&Y) staging scale and Unified Parkinson's Disease Rating Scale (UPDRS) part III. A longitudinal, linear mixed model was performed to compare the changes of H&Y staging scale, UPDRS motor score and UPDRS sub scores between the two groups.  

Findings: A total of 156 patients (41 PARK16 carriers and 115 non-carriers) were evaluated and followed up for up to 9 years. Using longitudinal linear mixed model analysis, there was a greater rate of deterioration in the motor function as measured by the UPDRS scores compared to non-carriers after 5 years from the date of diagnosis (p=0.007). In addition, we demonstrated that PARK16 variant carriers had worse gait scores (p=0.033) and greater motor progression than non-carriers after 6 years based on the modified H&Y staging scale (P=0.025).  

Interpretation: In a 9-year longitudinal study, we demonstrated that PD PARK16 variant carriers exhibited greater motor progression after 5 years of disease compared with non-carriers, suggesting that GWAS-linked gene variants may influence disease progression over time. Closer monitoring and management of these higher risk patients can facilitate better quality of life.  

Funding Statement: This research is supported by the Singapore National Research Foundation under its Translational and Clinical Research Flagship Programme.  

Declaration of Interests: The authors declare no competing financial interests.

Ethics Approval Statement: The Singhealth Centralized Institutional Review Board approved the study. All subjects gave written informed consent

Keywords: Parkinson Disease; Motor Progression; GWAS; Park 16

Suggested Citation

Deng, Xiao and Xiao, Bin and Allen Jr, John Carson and Ng, Yu-Lin and Foo, Jia-Nee and Lo, Yew-Long and Tan, Louis C. S. and Tan, Eng-King, Parkinson's Disease GWAS-linked Park16 Carriers Show Greater Motor Progression: A Longitudinal Study Over 9 Years (January 8, 2018). Available at SSRN: https://ssrn.com/abstract=3224874

Xiao Deng

Singapore General Hospital - Department of Neurology

Singapore, 169608
Singapore

Bin Xiao

Singapore General Hospital - Department of Neurology

Singapore, 169608
Singapore

John Carson Allen Jr

Duke-NUS Graduate Medical School Singapore

Singapore
Singapore

Yu-Lin Ng

Singapore General Hospital - Department of Neurology

Singapore, 169608
Singapore

Jia-Nee Foo

Agency for Science, Technology and Research (A*STAR) - Genome Institute of Singapore

60 Biopolis St
138672
Singapore

Yew-Long Lo

Singapore General Hospital - Department of Neurology

Singapore, 169608
Singapore

Louis C. S. Tan

Singapore General Hospital - Department of Neurology ( email )

Singapore, 169608
Singapore

National Neuroscience Institute - Department of Neurology

Singapore, 308433
Singapore

Eng-King Tan (Contact Author)

Singapore General Hospital - Department of Neurology ( email )

Singapore, 169608
Singapore

Duke-NUS Graduate Medical School Singapore

Singapore
Singapore

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