Two-sample Mendelian randomization analysis of 91 circulating inflammatory protein levels and meningioma

Meningiomas are prevalent central nervous system tumors with unclear etiological mechanisms. Due to their location outside the blood–brain barrier, they may be susceptible to systemic inflammatory responses. This study aimed to explore the causal relationship between 91 inflammatory proteins and meningiomas through 2-sample Mendelian randomization (MR). Using genome-wide association studies data from 14,824 participants, single nucleotide polymorphisms associated with inflammatory proteins were selected as instrumental variables. Meningioma data were obtained from a Finnish database (1316 cases and 3,13,392 controls). The inverse-variance weighted method assessed associations, with sensitivity analyses to ensure robustness. Reverse MR examined meningioma impact on inflammatory proteins. Forward MR analysis showed elevated Fms-related tyrosine kinase 3 ligand (FLT3L) levels correlated with reduced meningioma risk (OR = 0.72, 95% CI = 0.61–0.85, P < .001). Reverse MR suggested meningiomas might lower plasma FLT3L, C-X-C motif chemokine 11, adenosine deaminase, and hepatocyte growth factor levels. FLT3L may play a protective role in meningiomas, warranting further research on inflammatory proteins for prevention and treatment strategies.