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.