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.
Neurol Neuroimmunol Neuroinflamm. 2020 Nov 19;8(1). doi: 10.1212/NXI.0000000000000920. Print 2021 Jan.
To examine whether lifelong genetically increased serum urate levels, a potent antioxidant, contribute to MS susceptibility using Mendelian randomization (MR).
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.
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, = 0.76; MS2: OR = 0.99, 95% CI 0.89-1.11, = 0.90; MS3: OR = 1.00, 95% CI 0.98-1.2, = 0.91). Pleiotropy robust MR methods yielded consistent estimates.
This MR study does not support a clinically relevant causal effect of serum urate levels on the risk of MS.
利用孟德尔随机化（MR）研究终身遗传性血清尿酸水平升高（一种强效抗氧化剂）是否与多发性硬化症（MS）易感性有关。
本两样本 MR 研究纳入了一项全基因组关联研究荟萃分析中与血清尿酸水平密切相关的 25 个独立遗传变异，该研究共纳入了 140949 名个体。通过国际多发性硬化症遗传联合会的 3 个大型 MS 遗传数据集中的汇总统计数据，评估这些遗传变异对 MS 风险的影响，该数据共包含 61667 例 MS 病例和 86806 例对照。进行了多种敏感性分析，以评估 MR 的假设并排除潜在的多效性变异。
使用逆方差加权 MR，我们在任何队列中均未发现血清尿酸水平与 MS 风险之间存在因果关系的证据（MS1：尿酸每增加 1mg/dL 单位，MS 的比值比为 0.99，95%CI 0.89-1.08， = 0.76；MS2：OR = 0.99，95%CI 0.89-1.11， = 0.90；MS3：OR = 1.00，95%CI 0.98-1.2， = 0.91）。稳健性多效性 MR 方法得出了一致的估计值。
本 MR 研究不支持血清尿酸水平与 MS 风险之间存在临床相关的因果关系。
