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Mendelian randomization study shows no causal relationship between circulating urate levels and Parkinson's disease

Kia, DA; Noyce, AJ; White, J; Speed, D; Nicolas, A; IPDGC collaborators, .; Burgess, S; ... Wood, NW; + view all (2018) Mendelian randomization study shows no causal relationship between circulating urate levels and Parkinson's disease. Annals of Neurology , 84 (2) pp. 191-199. 10.1002/ana.25294. Green open access

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Abstract

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). INTERPRETATION: 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.

Type: Article
Title: Mendelian randomization study shows no causal relationship between circulating urate levels and Parkinson's disease
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/ana.25294
Publisher version: https://doi.org/10.1002/ana.25294
Language: English
Additional information: Copyright © 2018 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Health Informatics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Health Informatics > Clinical Epidemiology
URI: http://discovery.ucl.ac.uk/id/eprint/10053807
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