Bi-directional effects between inflammatory molecules and intracranial aneurysm

Area of Science:

• Genetics
• Cardiovascular Science
• Immunology

Background:

• Inflammation plays a role in intracranial aneurysm (IA) pathogenesis, but causal links are unclear.
• Investigating causality between circulating inflammatory molecules (IMs) and IA is crucial.

Purpose of the Study:

• To investigate the causal relationship between circulating inflammatory molecules (IMs) and intracranial aneurysms (IA) using bi-directional Mendelian randomization.

Main Methods:

• Bi-directional Mendelian randomization (MR) analysis using GWAS data from Finnish and Icelandic populations for IMs and European descent for IA.
• Colocalization and Venn analyses were performed to validate MR findings and identify overlapping causalities.

Main Results:

• No significant causality was found between candidate IMs and IA or its subtypes.
• RANTES showed a suggestive association with IA and aneurysmal subarachnoid hemorrhage (aSAH) in both Finnish and Icelandic models.
• Colocalization analysis provided limited evidence of shared genetic instruments, except for MCP3 and aSAH in the Icelandic model.

Conclusions:

• This study did not identify significant causal links between IMs and IA.
• RANTES may have a potential role in IA and aSAH development.
• Further research is needed to elucidate the role of IMs in IA pathogenesis.