Genetically Predicted Immune Cells Mediate the Association between HLA-B and Cerebral Atherosclerosis

Objective: Investigating the causal relationship between HLA Class l genes and cerebral atherosclerosis (CA) and identifying the role of immune cells as a potential mediator. Methods: The study conducted a Mendelian randomization (MR) study using an Inverse Variance Weighted (IVW) approach to investigate the causal role of HLA Class I genes in CA and the mediating effect of immune cells on this association. Results: MR Analysis determined that HLA-B (IVW: odds ratio (OR) = 1.4493, 95% confidence interval (CI) = 1.1296−1.8595, p = 0.0035) increased the risk of CA. In addition, 39 immune cell traits were associated with CA. Notably, the proportion of genetically predicted HLA-B mediated by Unsw Mem % lymphocyte was 13.1%. Conclusion: This study suggests a causal relationship between HLA-B and CA, possibly mediated by immune cells.