Background

Observational studies suggest that physical activity (PA) can independently modify the risk of developing multiple sclerosis (MS).

Objective

To investigate the causal effect of PA on MS by Mendelian randomization (MR) approaches.

Methods

Through a genome-wide association study including 91,105 participants from UK Biobank, we obtained 5 single-nucleotide polymorphisms (SNPs) associated with accelerometer-measured PA (P < 5 × 10⁻⁸). Summary-level data for MS were obtained from a meta-analysis, incorporating 14,802 subjects with MS and 26,703 healthy controls of European ancestry. MR analyses were performed using the inverse-variance-weighted method, weighted median estimator, and MR-PRESSO method. Additional analyses were further performed using MR-Egger intercept and Cochran’s Q statistic to verify the robustness of our findings.

Results

We failed to detect a causal effect of PA on MS (OR, 0.60; 95% confidence interval [CI], 0.30–1.20; P = 0.15) per in the random-effects IVW analysis. Additional MR methods yielded consistent results. MR-Egger regression suggested no evidence of horizontal pleiotropy (Intercept = 0.14, P = 0.21) and there seemed no substantial heterogeneity (I² = 29.8%, P = 0.22) among individual SNPs.

Conclusion

Our findings suggest that enhancing PA might not modify the risk of developing MS independent of established risk factors.

中文翻译：

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加速度计测量值与多发性硬化症之间的关系：2 样本孟德尔随机化研究

背景

观察性研究表明，体育锻炼 (PA) 可以独立地改变患多发性硬化症 (MS) 的风险。

客观的

通过孟德尔随机化 (MR) 方法研究 PA 对 MS 的因果影响。

方法

通过包括来自英国生物银行的 91,105 名参与者的全基因组关联研究，我们获得了 5 个与加速度计测量的 PA 相关的单核苷酸多态性 (SNP) ( P  < 5 × 10 ^-8 )。MS 的概要数据来自一项荟萃分析，纳入了 14,802 名 MS 受试者和 26,703 名欧洲血统的健康对照。使用逆方差加权方法、加权中值估计量和 MR-PRESSO 方法进行 MR 分析。使用 MR-Egger 截距和Cochran 的 Q 统计量进一步进行了额外的分析，以验证我们发现的稳健性。

结果

 在随机效应 IVW 分析中，我们未能检测到 PA 对 MS 的因果效应（OR，0.60；95% 置信区间 [CI]，0.30–1.20；P = 0.15）。其他 MR 方法产生了一致的结果。MR-Egger 回归表明没有水平多效性的证据（截距 = 0.14，P  = 0.21），并且 单个 SNP 之间似乎没有实质性的异质性（I ²  = 29.8%，P = 0.22）。

结论

我们的研究结果表明，独立于既定风险因素，增强 PA 可能不会改变发生 MS 的风险。