Objective: To investigate the causal relationship between circulating serum urate levels and the risk of Parkinson’s disease (PD) using a two-sample Mendelian randomization (MR) approach.
Background: Observational studies have suggested that higher serum urate levels may be associated with a reduced risk of PD, potentially due to antioxidant and neuroprotective properties. However, these associations are susceptible to confounding and reverse causation, and causal evidence remains limited.
Method: We conducted a two-sample MR analysis using genetic instruments strongly associated with serum urate levels identified from large-scale genome-wide association studies (GWAS). Summary statistics for PD were obtained from the International Parkinson’s Disease Genomics Consortium (IPDGC). The inverse-variance weighted (IVW) method was used as the primary analysis, complemented by weighted median, MR-Egger regression, and MR-PRESSO to assess robustness and horizontal pleiotropy.
Results: Genetically predicted higher serum urate levels were causally associated with a lower risk of PD (OR per 1-SD increase = 0.78, 95% CI: 0.68–0.90, P = 0.001). Results were consistent using the weighted median method (OR = 0.81, 95% CI: 0.70–0.94, P = 0.006). MR-Egger regression showed a similar direction of effect, though with reduced precision (OR = 0.85, 95% CI: 0.65–1.10, P = 0.21). There was no evidence of directional pleiotropy based on the MR-Egger intercept test (P = 0.34), and MR-PRESSO did not identify any significant outlier variants influencing the results.
Conclusion: This Mendelian randomization study provides genetic evidence supporting a protective causal role of higher circulating serum urate levels in PD risk. These findings strengthen the biological rationale for targeting oxidative stress–related pathways in PD prevention and suggest that urate-related metabolic pathways may represent potential therapeutic or stratification targets in early-stage PD.
To cite this abstract in AMA style:
P. Tang, Y. Liu. Urate Levels and Risk of Parkinson’s Disease：A Two-Sample Mendelian Randomization Study [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/urate-levels-and-risk-of-parkinsons-disease%ef%bc%9aa-two-sample-mendelian-randomization-study/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/urate-levels-and-risk-of-parkinsons-disease%ef%bc%9aa-two-sample-mendelian-randomization-study/