Mendelian randomization study shows no causal effects of serum urate levels on the risk of MS

Adil Harroud; J Brent Richards; Sergio E Baranzini

doi:10.1212/NXI.0000000000000920

Mendelian randomization study shows no causal effects of serum urate levels on the risk of MS

Neurol Neuroimmunol Neuroinflamm. 2020 Nov 19;8(1):e920. doi: 10.1212/NXI.0000000000000920. Print 2021 Jan.

Authors

Adil Harroud¹, J Brent Richards¹, Sergio E Baranzini²

Affiliations

¹ From the Department of Neurology (A.H., S.E.B.), University of California San Francisco, California; Weill Institute for Neurosciences (A.H., S.E.B.), University of California San Francisco, California; Centre for Clinical Epidemiology (J.B.R.), Department of Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada; Department of Human Genetics (J.B.R.), McGill University, Montreal, Quebec, Canada; Department of Medicine (J.B.R.), McGill University Montreal, Quebec, Canada; Department of Epidemiology (J.B.R.), Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada; Department of Twin Research and Genetic Epidemiology (J.B.R.), King's College London, United Kingdom; Institute for Human Genetics (S.E.B.), University of California San Francisco, California; and Bakar Computational Health Sciences Institute (S.E.B.), University of California San Francisco, California.
² From the Department of Neurology (A.H., S.E.B.), University of California San Francisco, California; Weill Institute for Neurosciences (A.H., S.E.B.), University of California San Francisco, California; Centre for Clinical Epidemiology (J.B.R.), Department of Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada; Department of Human Genetics (J.B.R.), McGill University, Montreal, Quebec, Canada; Department of Medicine (J.B.R.), McGill University Montreal, Quebec, Canada; Department of Epidemiology (J.B.R.), Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada; Department of Twin Research and Genetic Epidemiology (J.B.R.), King's College London, United Kingdom; Institute for Human Genetics (S.E.B.), University of California San Francisco, California; and Bakar Computational Health Sciences Institute (S.E.B.), University of California San Francisco, California. sergio.baranzini@ucsf.edu.

Abstract

Objective: To examine whether lifelong genetically increased serum urate levels, a potent antioxidant, contribute to MS susceptibility using Mendelian randomization (MR).

Methods: This 2-sample MR study included 25 independent genetic variants strongly associated with serum urate levels in a genome-wide association study meta-analysis of 140,949 individuals. Effects on the risk of MS were assessed with summary statistics from 3 large-scale MS genetic data sets totaling 61,667 MS cases and 86,806 controls from the International MS Genetic Consortium. Multiple sensitivity analyses were performed to evaluate the assumptions of MR and remove potentially pleiotropic variants.

Results: Using inverse-variance weighted MR, we found no evidence for a causal effect of serum urate level on the risk of MS in any of the cohorts (MS1: OR 0.99 per each mg/dL unit increase in urate, 95% CI 0.89-1.08, p = 0.76; MS2: OR = 0.99, 95% CI 0.89-1.11, p = 0.90; MS3: OR = 1.00, 95% CI 0.98-1.2, p = 0.91). Pleiotropy robust MR methods yielded consistent estimates.

Conclusion: This MR study does not support a clinically relevant causal effect of serum urate levels on the risk of MS.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Genome-Wide Association Study
Humans
Mendelian Randomization Analysis
Multiple Sclerosis / blood*
Multiple Sclerosis / genetics*
Uric Acid / blood*

Substances

Uric Acid

Abstract

Publication types

MeSH terms

Substances

Grants and funding