Plasma tissue factor as a promising marker in multiple sclerosis: Evidence from a two-sample Mendelian randomization
Rui Pan1, Aiqi Wang2, Yaqi Li1
1School of Nursing, Huizhou Health Sciences Polytechnic, Huizhou, Guangdong, P. R. China.
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.
Insights
This study found that higher tissue factor (TF) levels are associated with an increased risk of multiple sclerosis (MS). TF may serve as a potential biomarker and therapeutic target for MS.
Area of Science:
- Neuroimmunology
- Hematology
- Genetics
Background:
- Multiple sclerosis (MS) is a central nervous system demyelinating disease.
- The coagulation pathway is implicated in MS pathogenesis, but causal links remain unclear.
Purpose of the Study:
- To investigate the causal association between plasma coagulation factors and the risk of multiple sclerosis.
- To identify potential biomarkers for MS.
Main Methods:
- A two-sample Mendelian randomization (MR) analysis was performed.
- Genetic variants for plasma coagulation factors were used as instrumental variables.
- Summary statistics from a large genome-wide association study for MS were utilized.
Main Results:
- Elevated plasma tissue factor (TF) levels showed a causal association with an increased risk of MS onset (OR: 1.215, P < 0.001).
- Sensitivity analyses confirmed the association between TF and MS risk.
- No significant causal associations were found for other plasma coagulation factors with MS.
Conclusions:
- Tissue factor (TF) is suggestively associated with multiple sclerosis (MS).
- Increased plasma TF levels correlate with higher MS risk.
- TF presents a promising biomarker and potential therapeutic target for MS.
