Integrating genome-wide association studies and transcriptomics prioritizes drug targets for meningioma.

Abstract

Meningioma, a prevalent central nervous system tumour, presents a significant challenge in neuro-oncology. This study harnesses genome-wide association studies (GWAS) and transcriptomic analysis to illuminate the pathological underpinnings of meningioma and spearhead the discovery of novel drug targets. By employing summary-data-based Mendelian randomization (SMR), colocalization analyses and Mendelian randomization, we pinpointed four genes as pivotal therapeutic targets. The integration of bulk and single-cell RNA sequencing confirmed the upregulated expression of three of the genes (XBP1, TTC28 and TRPC6) in meningioma tissues, unravelling their cellular distribution and hinting at the tumour's intrinsic heterogeneity. Molecular docking further identified dexamethasone and levonorgestrel as potential modulators of these targets, paving the way for personalized meningioma treatment strategies. This research advances our understanding of meningioma's molecular landscape and illustrates the power of genomic and transcriptomic integration in the realm of precision oncology.