Investigating Potential Drug Targets in Intracranial Aneurysms through Mendelian Randomization and Transcriptome Analyses

Background: Intracranial aneurysms represent one of the most common and life-threatening vascular diseases. Transcriptomics and immune cell infiltration have been shown to be critical in the occurrence and progression of intracranial aneurysms. This study aimed to investigate the key genes and immune mechanisms involved in intracranial aneurysms through bioinformatics analysis and Mendelian randomization (MR) validation. Methods: Gene microarray datasets were obtained from the gene expression synthesis (GEO) public website. By integrating CIBERSORT, weighted gene co-expression network analysis (WGCNA), and differentially expressed genes (DEGs), we identified key genes associated with intracranial aneurysms and having the highest intracranial aneurysm connectivity. Subsequently, PPI was used to further explore the key genes. Major biological functions and signaling pathways were elucidated through gene ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Then, immunoinfiltration analysis of intracranial aneurysms and pivotal genes was performed. Finally, MR was performed to explore the immune mechanisms associated with intracranial aneurysms. Results: We identified the hub gene TTK through the GEO database, WGCNA, and PPI. The nomogram showed that TTK exhibited a higher risk, the area under the receiver operating characteristic curve was greater than 0.8, and the diagnostic accuracy of TTK was higher. Immunoinfiltration confirmed that natural killer (NK) cells might be related to intracranial aneurysms and the TTK gene, and MR confirmed that absolute NK cell count was significantly related to intracranial aneurysms. Conclusion: Our study suggests that TTK may be involved in the progression of intracranial aneurysms through the absolute count of pro-inflammatory NK cells. Thus, TTK may be a prognostic biomarker and intervention target for intracranial aneurysm.