Pan Rui, Wang Aiqi, Li Yaqi, Xie Qizhi, Lin Meihua, Li Jiayi, Shi Xiaolei
School of Nursing, Huizhou Health Sciences Polytechnic, Huizhou, Guangdong, P. R. China.
School of Pharmacy and Laboratory, Huizhou Health Sciences Polytechnic, Huizhou, Guangdong, P. R. China.
Transl Neurosci. 2025 Aug 16;16(1):20250378. doi: 10.1515/tnsci-2025-0378. eCollection 2025 Jan 1.
Multiple sclerosis (MS) is a major demyelinating disorder that affects the central nervous system. A growing body of evidence has revealed the involvement of coagulation pathway in the pathogenesis of MS. However, the causal association between coagulation factors and MS is still unclear.
A two-sample Mendelian randomization (MR) analysis was conducted. Genetic variants for plasma coagulation factors were identified as instrumental variables. Summary-level statistics for MS were collected from a large-scale genome-wide association study, including 47,429 cases and 68,374 controls. Primary MR analysis was performed using the inverse-variance weighting (IVW) approach. False discovery rate (FDR)-adjusted method was applied to adjust for multiple testing. MR-Egger, weighted median, simple mode, weighted mode, and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods were used as sensitivity analysis approaches.
A causal effect of higher plasma tissue factor (TF) levels on the risk of MS onset was identified using IVW method (OR: 1.215, 95% CI 1.108-1.333, < 0.001, < 0.001). Complementary analysis using weighted median (OR: 1.262, 95% CI: 1.119-1.423, < 0.001), weighted mode (OR: 1.238, 95% CI: 1.100-1.394, = 0.012), and MR-PRESSO (OR: 1.215, 95% CI: 1.125-1.313, = 0.003) methods yielded consistent results. Null associations were found for other plasma coagulation factors with MS.
The study demonstrates a suggestive association between TF and MS. Increasing plasma TF was associated with an increase in MS risk. TF should be a promising biomarker and new target for MS.
多发性硬化症（MS）是一种影响中枢神经系统的主要脱髓鞘疾病。越来越多的证据表明凝血途径参与了MS的发病机制。然而，凝血因子与MS之间的因果关系仍不清楚。
进行了两样本孟德尔随机化（MR）分析。将血浆凝血因子的基因变异确定为工具变量。从一项大规模全基因组关联研究中收集MS的汇总统计数据，包括47429例病例和68374例对照。使用逆方差加权（IVW）方法进行主要MR分析。应用错误发现率（FDR）调整方法对多重检验进行调整。采用MR-Egger、加权中位数、简单模式、加权模式和MR-多效性残差和异常值（MR-PRESSO）方法作为敏感性分析方法。
使用IVW方法确定血浆组织因子（TF）水平升高对MS发病风险有因果效应（OR：1.215，95%CI 1.108-1.333，<0.001，<0.001）。使用加权中位数（OR：1.262，95%CI：1.119-1.423，<0.001）、加权模式（OR：1.238，95%CI：1.100-1.394，=0.012）和MR-PRESSO（OR：1.215，95%CI：1.125-1.313，=0.003）方法进行的补充分析得出了一致的结果。未发现其他血浆凝血因子与MS之间存在关联。
该研究表明TF与MS之间存在提示性关联。血浆TF升高与MS风险增加相关。TF应该是MS一个有前景的生物标志物和新靶点。
