A Two-way Mendelian randomisation study of inflammatory factors and the risk of meningioma

Abstract Objectives To explore the causal relationship between inflammatory factors and meningioma. Methods The inverse variance weighting method (IVW), Mendelian Randomisation Egger (MR-Egger) regression, weighted median method, simple mode method, and weighted mode method were used to analyse the potential causal relationship between exposure factors and outcomes. Results Preliminary MR analysis showed that 6 inflammatory factors, including C-C motif chemokine 19 levels, osteoprotegerin levels, Fms-related tyrosine kinase 3 (FLT3) ligand levels, matrix metalloproteinase-1 levels, C-C motif chemokine 28 levels, and interleukin-5 levels, were associated with meningiomas. Further screening of inflammatory factors and positive MR analysis showed that FLT3 ligand levels had a clear causal association with the occurrence of meningioma (odds ratio [OR]=0.713, 95 % confidence interval [CI]: 0.598–0.851). The results of reverse MR analysis showed that there was a clear causal association between meningioma and Fms-related tyrosine kinase 3 ligand levels (OR=0.936, 95 % CI: 0.885–0.990). The results of heterogeneity and pleiotropic tests of MR-Egger intercept showed that there was no heterogeneity or pleiotropy in all data. Conclusions This study clarified FLT3 as being involved in the pathogenesis of meningioma from a genetic perspective and genetically predicted lower FLT3L to be causally associated with a higher meningioma risk, implicating FLT3 signalling in meningioma pathogenesis. FLT3 as a genetically supported candidate factor associated with meningioma risk.