Causal role of immune cells in ischemic stroke: a Mendelian Randomization study

Abstract Background Conventional observational designs face challenges in studying this relationship, as confounding factors, reverse causality, minor exposure factors and multiple tests cannot be completely eliminated. There is currently a lack of MR studies concerning immune cells and the risk of ischemic stroke. This particular study offers a novel perspective on risk prediction for ischemic stroke. Objective To investigate the causal relationship between immune cells and ischemic stroke through Mendelian randomization analysis. Methods A complete two-sample Mendelian randomization (MR) analysis was utilized to ascertain the causative relationship between immune cells and ischemic stroke. Using publicly available genetic data, we investigated the causal association between 731 immune cells and the risk of ischemic stroke. Four immune characteristics were included: relative cells (RC), absolute cells (AC), median fluorescence intensity (MFI), and morphological parameters (MP). MR-Egger, Weighted median, Inverse variance weighted (IVW), Weighted mode, Simple mode, and MRPRESS were utilized for analysis. Heterogeneity and horizontal pleiotropy tests were also conducted. Results Mendelian randomization analysis showed that 32 of the 731 immune cells had a robust causal relationship with ischemic stroke, among which 15 immune cells such as IgD−CD27− %B cell (β = 0.033, 95%CI = 1.002 ~ 1.065, p = 0.037), IgD+ CD24 + AC (β = 0.045, 1.010 ~ 1.082, p = 0.012), CD25hi CD45RA−CD4 not Treg %T cell (β = 0.022, 95%CI = 1.002 ~ 1.042, p = 0.028) and soon. CD62L−HLADR++ monocyte AC (β =-0.053, 95% CI = 0.914 ~ 0.985, p = 0.005), CD33br HLA DR+ CD14− AC (β =-0.017, 95% CI = 0.972 ~ 0.995, p = 0.004), EM DN (CD4−CD8−) %DN (β =-0.014, 95% CI = 0.975 ~ 0.997, p = 0.014), etc. There exists a strong inverse causal link for ischemic stroke. Conclusion Our study has demonstrated a close genetic link between immune cells and ischemic stroke. Fifteen immune cells such as IgD−CD27− %B cell, IgD+ CD24+ AC, CD25hi CD45RA−CD4 not Treg %T cell have robust positive causal associations with ischemic stroke, and seventeen immune cells such asCD62L− HLA DR++ monocyte AC, CD33br HLA DR+ CD14− AC, EM DN (CD4−CD8−) %DN have robust positive causal associations with ischemic stroke. A strong inverse causal relationship with ischemic stroke offers direction for forthcoming clinical studies.