Plasma tissue factor as a promising marker in multiple sclerosis: Evidence from a two-sample Mendelian randomization study.

Background: 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.

Method: 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.

Results: 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, P < 0.001, P _FDR < 0.001). Complementary analysis using weighted median (OR: 1.262, 95% CI: 1.119-1.423, P < 0.001), weighted mode (OR: 1.238, 95% CI: 1.100-1.394, P = 0.012), and MR-PRESSO (OR: 1.215, 95% CI: 1.125-1.313, P = 0.003) methods yielded consistent results. Null associations were found for other plasma coagulation factors with MS.

Conclusions: 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.