Genetic association between epilepsy and gliomas: Insights from Mendelian randomization and single-cell transcriptomic analyses

Background

Seizures are prevalent in glioma patients, especially in those with low-grade gliomas. The interaction between gliomas and epilepsy involves complex biological mechanisms that are not fully understood.

Methods

We collected Genome-Wide Association Study data for epilepsy and gliomas, performed differential expression analysis, and conducted Gene Ontology (GO) enrichment analysis on the identified genes. Single-cell RNA sequencing data (scRNA-seq) from GSE221534 dataset in Gene Expression Omnibus (GEO) were used to analyze cell–cell interactions within glioma samples from patients with and without epilepsy.

Results

Mendelian Randomization (MR) analysis revealed significant associations between genetic variants related to epilepsy and glioma risk, suggesting a potential causal relationship, especially in astrocytomas. Differential expression analysis identified epilepsy-related genes that were significantly upregulated in astrocytoma tissues compared to normal brain tissues. GO enrichment analysis indicated that these genes are involved in critical biological processes such as neurogenesis and cellular signaling. The scRNA-seq analysis showed, compared to non-epileptic samples, glioma stem cells, microglia, and NK cells are increased in the core regions of astrocytomas in epileptic patients. Additionally, intercellular communication between tumor cells and other non-tumor cells is markedly enhanced in astrocytoma samples from epileptic patients.

Conclusion

This study provides evidence of a genetic association between epilepsy and gliomas and elucidates the biological mechanisms through which epilepsy may influence glioma progression.