The role of immune cell phenotypes and metabolites in the risk of ischemic stroke: a Mendelian randomization-based mediation analysis

BackgroundIschemic stroke (IS) occurs when a blood clot obstructs a blood vessel supplying blood to the brain, leading to brain tissue damage due to insufficient oxygen and nutrients. The roles of immune cells and metabolites in IS are increasingly recognized, yet their specific mechanisms remain unclear.MethodsThis study conducted a comprehensive statistical analysis to explore the relationships between immune cell phenotypes, metabolite levels, and IS. We utilized methods such as inverse variance weighted (IVW), weighted median, and MR Egger to ensure robust results. Sensitivity analyses were performed to confirm the absence of significant heterogeneity or pleiotropy.ResultsWe identified several immune cell phenotypes significantly associated with IS. Notably, IgD + CD24 + AC showed a positive association with IS (OR = 1.045601, p = 0.011562), while CD62L- HLA DR + + monocyte AC demonstrated a negative association (OR = 0.948673, p = 0.005415). Among metabolites, adenosine 5'-monophosphate (AMP) to cysteine ratio was positively associated with IS (OR = 1.083144, p = 0.000310), whereas xanthurenate levels were negatively associated (OR = 0.926100, p = 0.001614). Mediation analysis revealed a significant mediating effect of acetylcarnitine levels on the relationship between IgD + CD24 + AC and IS, with an estimated mediation effect of 0.00606 (p = 0.036834077).ConclusionOur study highlights the crucial roles of specific immune cell phenotypes and metabolites in IS, suggesting their potential as novel therapeutic targets or biomarkers. The mediation analysis underscores the complex interactions between immune cells and metabolites in IS, providing valuable insights for future research. These findings pave the way for further exploration of the pathophysiological mechanisms and therapeutic strategies for IS.