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Publication Detail
Mendelian randomization study shows no causal relationship between circulating urate levels and Parkinson's disease
  • Publication Type:
    Journal article
  • Publication Sub Type:
  • Authors:
    Kia DA, Noyce AJ, White J, Speed D, Nicolas A, IPDGC collaborators , Burgess S, Lawlor DA, Davey Smith G, Singleton A, Nalls MA, Sofat R, Wood NW
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  • Publication date:
  • Journal:
    Annals of Neurology
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  • Keywords:
    IPDGC collaborators
  • Addresses:
    Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
Observational studies have shown that increased plasma urate is associated with lower risk of Parkinson's Disease (PD), but these studies were not designed to test causality. If a causal relationship exists, then modulating plasma urate levels could be a potential preventive avenue for PD. We used a large two-sample Mendelian randomization (MR) design to assess for a causal relationship between plasma urate and PD risk.We used a genetic instrument consisting of 31 independent loci for plasma urate on a case-control genome-wide association study dataset which included 13,708 PD cases and 95,282 controls. Individual effect estimates for each SNP were combined using the inverse-variance weighted (IVW) method. Two additional methods, MR-Egger and a penalized weighted median based (PWM) approach, were used to assess potential bias due to pleiotropy or invalid instruments.We found no evidence for a causal relationship between urate and PD, with an effect estimate from the IVW method of OR 1.03 (95% CI 0.88-1.20) per 1 SD increase in plasma urate levels. MR Egger and PWM analyses yielded similar estimates (OR 0.99 [95% CI 0.83-1.17] and 0.99 [95% CI 0.86-1.14], respectively).We do not find evidence for a linear causal protective effect by urate on PD risk. The associations observed in previous observational studies may be in part due to confounding or reverse causality. In the context of the present findings, strategies to elevate circulating urate levels may not reduce overall PD risk. This article is protected by copyright. All rights reserved.
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