Serum EpCAM or PECAM Levels and Risk of Ischemic Stroke: A Two-Sample Mendelian Randomization Study

Elevated serum Epithelial cell adhesion molecule (EpCAM) or Platelet endothelial cell adhesion molecule (PECAM) are associated with ischemic stroke (IS), but the causality remains unclear. A two-sample Mendelian randomization (MR) study was performed to examine the causal effect of serum EpCAM or PECAM levels on the risk of IS subtypes.The study utilized GWAS datasets from European and African American populations to identify SNPs associated with serum EpCAM and PECAM levels as instrumental variables. These were then used in MR analyses for IS subtypes, employing multiple methods including IVW, weighted median, MR-Egger, and maximum likelihood. Sensitivity analyses were conducted to validate the results. No significant causal association was observed for EpCAM levels with any of three IS subtypes. Main IVW MR analysis indicated that serum PECAM levels were negatively related to the incidence of large artery stroke (LAS), small vessel stroke (SVS), and cardioembolic stroke (CES), especially CES. Sensitivity analyses confirmed the robustness of these results. Our study reveals a negative correlation between genetically predicted PECAM levels and ischemic stroke risk, particularly for cardioembolic stroke, suggesting PECAM's potential as a biomarker for risk stratification. While no clear causal relationship was found for EpCAM, these findings have significant implications for stroke prevention and treatment strategies. Further research is needed to validate these results and explore their clinical applications, potentially leading to more personalized approaches in stroke management.