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

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