Causal association between immune cells and meningeoma based on bidirectional two-sample Mendelian randomization analysis

WANG Geyu; SUN Yingwei; SUN Xiaoyu; CHEN Ligang; LI Xinning; FENG Sizhe

Abstract：Objective To explore the potential causal relationship between immune cells and the risk of meningioma.Methods Based on publicly available genome-wide association study(GWAS)summary statistics of immune cells and meningioma,this study employed the Mendelian randomization(MR)approach to investigate the causal relationship between circulating immune cells and the risk of meningioma.Causal effects were primarily evaluated using the inverse-variance weighted(IVW)method,with supplementary analyses conducted by using Bayesian weighted Mendelian randomization(BWMR)to provide additional insights into the causal relationship.The robustness and reliability of the results were assessed through leave-one-out analysis,heterogeneity testing,and horizontal pleiotropy testing.Results MR analysis,combined with BWMR and adjusted for false discovery rate(FDR),identified significant associations between six immune cell types and the risk of meningioma(P<0.05).The results indicated that CD62L-monocyte AC(OR=0.921,95%CI 0.875-0.969,P=0.001)、CD86+myeloid DC AC(OR=0.930,95%CI 0.888-0.973,P=0.002),and CD38 on IgD+CD38br(OR=0.889,95%CI 0.833-0.950,P=0.0005)may reduce the risk of benign meningioma.CD25hi CD45RA-CD4 not Treg%T cell(OR=0.919,95%CI 0.862-0.98,P=0.011),CD86 on myeloid DC(OR=0.822,95%CI 0.715-0.945,P=0.006),and CD45 on CD66b++myelod cell(OR=0.853,95%CI 0.772-0.943,P=0.002)may reduce the risk of malignant meningioma.Cochran's Q test revealed no heterogeneity,MR-PRESSO analysis identified no outliers,and MR-Egger intercept test indicated no evidence of horizontal pleiotropy.The leave-one-out analysis supported the robustness of the findings.Conclusions Certain immune cell phenotypes may serve as predictive markers for the clinical diagnosis of meningioma and the development of new immunotherapeutic strategies.