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

Annals of Neurology
Demis A KiaNicholas W Wood

Abstract

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 data set, 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 (PWM)-based approach, were used to assess potential bias attributed 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 odds ratio (OR) 1.03 (95% confidence interval [CI], 0.88-1.20) per 1-standard-deviation 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], respecti...Continue Reading

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Citations

Jul 18, 2018·Annals of Neurology·Inke R König, Fabiola M Del Greco
Feb 15, 2019·Annals of Neurology·Rachit BakshiMichael Schwarzschild
Aug 7, 2019·Circulation Research·Fang FangDaniela Mariosa
Nov 13, 2019·Annals of Clinical and Translational Neurology·Yun ShenXiang Gao
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Nov 21, 2020·Neurology. Neuroimmunology and Neuroinflammation·Adil HarroudSergio E Baranzini
Jan 29, 2020·Neurobiology of Disease·Sara Bandres-CigaAndrew B Singleton

Related Concepts

Parkinson Disease
Urate
Variation (Genetics)
Viral Markers
Single Nucleotide Polymorphism
Online Mendelian Inheritance In Man
Mendelian Randomization Analysis
Plasma
Hemoglobin Ann Arbor
Instrument - Device

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