Causal relations between immune cells and cerebral hemorrhage: a bidirectional Mendelian randomization study.

Abstract

Background: Previous studies have shown that an increased number of immune cells is closely associated with the onset and course changes of intracerebral hemorrhage, but the exact causal relationship has not been clarified. The proposed study. The aim of this study was to investigate the causal relationship between immune cells and intracerebral hemorrhage by a two-way Mendelian randomization method.

Methods: Two sets of SNPs strongly associated with intracerebral hemorrhage were used as instrumental variables, and two-way Mendelian randomization analyses were performed using MR-egger regression, random-effects inverse variance weighting, and Cochran's Q test, funnel plot, and leave-one-out method were used to assess the validity and heterogeneity of the included genetic variation instruments. The level of multiplicity and heterogeneity of the included genetic variance instruments was assessed using Cochran's Q test, funnel plot and "leave-one-out" method.

Results: The results analyzed by MR showed a clear causal relationship between three immune cells and intracerebral hemorrhage, and no heterogeneity between SNPs related to intracerebral hemorrhage, while scatterplot and funnel plot confirmed that the causality was less likely to be biased; MR-Egger results suggested that no genetic pleiotropy was found . Leave-one-out analysis was applied to suggest that the MR analysis results for a single SNP were robust; meanwhile, Meta-analysis was applied to combine the two intracerebral hemorrhage datasets, and the post hoc analysis results suggested that in the fixed-effects model and random-effects model, the immunocyte CD66b on Granulocytic Myeloid-Derived Suppressor Cells and other three immune cells were significantly causally associated with intracerebral hemorrhage, while the heterogeneity test suggested that there was no significant difference between the different datasets.

Conclusions: The present study found a significant causal relationship between specific immune cell phenotypes and intracerebral hemorrhage by Mendelian randomization analysis.