Dissecting the causal role of immunophenotypes in brain meningioma risk: A Mendelian randomization study

Meningiomas are primarily benign brain tumors that, despite their typically slow growth, often cause significant health issues due to their location. Emerging immunotherapy approaches have sparked optimism regarding treatment outcomes for patients. We conducted a comprehensive Mendelian randomization (MR) analysis, utilizing 731 immune cell phenotypes to explore causal relationships with Brain Meningioma. We employed inverse variance weighted as the primary analysis method, MR-Egger and Maximum likelihood as secondary methods, and Weighted median, Weighted mode, and Simple mode as supplementary methods to ascertain causal links. Additionally, we performed sensitivity tests including heterogeneity tests, pleiotropy tests, reverse MR, leave-one-out analysis, and MR-PRESSO to ensure result robustness. Our study identified potential causal relationships of 7 immune phenotypes with Brain Meningioma, comprising 2 risk factors and 5 protective factors. Specifically, B cell-related phenotypes included CD20 on IgD - CD24 - B cell (P = .048, OR = 1.094, 95% CI = 1.001 - 1.196), CD38 on IgD - CD38 + B cell (P = .004, OR = 0.949, 95% CI = 0.915 - 0.984), and CD38 on IgD - CD38dim B cell (P = .02, OR = 1.073, 95% CI = 1.011 - 1.140). T cell-related phenotypes included Activated CD4 regulatory T cell %CD4 + T cell (P = .013, OR = 0.885, 95% CI = 0.804 - 0.974) and CD25++ CD45RA - CD4 not regulatory T cell %CD4 + T cell (P = .004, OR = 0.905, 95% CI = 0.846 - 0.969). Monocyte-related phenotypes included CD39 on monocyte (P = .022, OR = 0.948, 95% CI = 0.905 - 0.992), and dendritic cell-related phenotype included CD86 + myeloid dendritic cell absolute count (P = .01, OR = 0.914, 95% CI = 0.853 - 0.979).