Immune Cells and Intracerebral Hemorrhage: A Causal Investigation Through Mendelian Randomization

Background

The involvement of immune cells in the pathophysiology of intracerebral hemorrhage (ICH) is becoming increasingly recognized, yet their specific causal contributions remain uncertain. The objective of this research is to uncover the potential causal interactions between diverse immune cells and ICH using Mendelian randomization (MR) analysis.

Methods

Genetic variants associated with 731 immune cell traits were sourced from a comprehensive genome-wide association study (GWAS) involving 3757 participants. Summary statistics data for ICH were acquired from FinnGen, comprising 4056 ICH cases and 371,717 controls. The principal analytical tool utilized in our study was the inverse-variance weighted (IVW) method, incorporated as a key component of a two-sample MR approach. To mitigate potential biases and verify the stability of the conclusions drawn from the primary analytical methods, a series of sensitivity analyses were performed.

Results

MR analysis elucidated 33 immune cell traits with causal associations, comprising B cells (eight traits), conventional dendritic cells (cDC, two traits), maturation stages of T cells (two traits), monocytes (two traits), myeloid cells (five traits), TBNK cells (six traits), and regulatory T cells (Treg, eight traits). DP (CD4+CD8+) %T cell (OR = 0.83, CI = 0.72–0.96, p = 0.013) exhibited the strongest protective effect. In contrast, transitional AC (OR = 1.09, CI = 1.02–1.16, p = 0.006) and IgD− CD27− %lymphocyte (OR = 1.08, CI = 1.00–1.17, p = 0.045) showed a higher tendency to increase the ICH risk. The sensitivity analyses validated the robustness and consistency of these results.

Conclusion

Our research provides robust evidence substantiating the causal relationship between specific immunophenotypes and ICH risk. The identification of these findings significantly enhances our understanding of the pathogenic mechanisms underlying ICH, particularly pertaining to the immune system. This breakthrough paves the way for innovative clinical and pharmaceutical research opportunities, potentially promoting the development of targeted therapies and enhanced strategies for managing and preventing ICH.