Bi-directional effects between inflammatory molecules and intracranial aneurysm.

Abstract

Although inflammation is closely associated with the pathogenesis of intracranial aneurysm (IA), detailed causal associations remain unclear. This study aimed to investigate the causality between circulating inflammatory molecules (IMs) and IA. The bi-directional Mendelian randomization (MR) analysis was conducted using two genome-wide association studies (GWAS) for inflammatory molecules (IMs) from Finnish and Icelandic populations, as well as GWAS datasets of IA cases and controls of European descent. Colocalization analysis was performed to validate MR associations. Subsequently, Venn analysis was conducted to identify the overlapped causalities. Integrating the findings from two MR models, RANTES was suggestively associated with IA (Finnish model: inverse variance-weighted odds ratio [ORIVW] (95% confidence interval [95% CI]), 0.86 (0.74-0.99); Icelandic model: 0.80 (0.68-0.94)) and aneurysmal subarachnoid hemorrhage (aSAH) (ORIVW (95% CI): 0.81 (0.68-0.95) and 0.80 (0.66-0.97) in Finnish and Icelandic models). IA and its subtypes were not associated with any of candidate IMs. However, colocalization analysis failed to identify significant evidence of shared genetic instruments between the exposures and outcomes, except for the MCP3-aSAH pair in the Icelandic model. No significant causality was identified between IMs and IA or their subtypes. RANTES is potentially associated with IA and aSAH. Further investigation is warranted to explore the role of IMs in IA development.