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Mendelian Randomisation Finds No Causal Association between Urate and Parkinson's Disease Progression

Rachel Coneys, Catherine S. Storm, Demis A. Kia, Mona Mohammad Almramhi, Nicholas Wood

2021Movement Disorders15 citationsDOI

Abstract

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative movement disorder. Observational studies suggest higher levels of plasma urate may protect against Parkinson's risk and progression; however, causality cannot be established. OBJECTIVES: This study set out to determine whether there is a true causal association between urate levels and PD age at onset (AAO) and progression severity using recently released PD AAO and progression genome-wide association study (GWAS) data. METHODS: A large two-sample Mendelian randomization design was employed, using genetic variants underlying urate levels and the latest GWAS data for PD outcomes. RESULTS: This study found no causal association between urate levels and Parkinson's risk, AAO, or progression severity. CONCLUSIONS: Our results predict increasing urate levels as a therapeutic strategy is unlikely to benefit PD patients. © 2021 International Parkinson and Movement Disorder Society.

Topics & Concepts

Mendelian randomizationGenome-wide association studyParkinson's diseaseObservational studyGenetic associationMedicineCausality (physics)Internal medicineDiseaseOncologyPsychologyBioinformaticsGeneticsBiologyGenetic variantsGenotypeSingle-nucleotide polymorphismGenePhysicsQuantum mechanicsGout, Hyperuricemia, Uric AcidThyroid Disorders and TreatmentsCardiovascular, Neuropeptides, and Oxidative Stress Research