Mendelian randomization and transcriptomic analysis reveal a relationship between subarachnoid hemorrhage and...

Area of Science:

• Neuroscience
• Genetics
• Biochemistry

Background:

• Post-translational modifications (PTMs) are critical regulators in stroke-induced brain injury.
• The specific roles of PTMs in subarachnoid hemorrhage (SAH) pathogenesis remain unclear.

Purpose of the Study:

• To identify PTM-associated genes involved in SAH.
• To determine causal PTM genes and biomarkers for SAH risk.
• To explore therapeutic strategies for SAH.

Main Methods:

• Differential gene expression analysis and PTM gene intersection.
• Mendelian randomization (MR) for causal inference.
• Machine learning for biomarker screening and diagnostic model development.
• Independent dataset validation and clinical correlation.
• Drug repurposing analysis via molecular docking and dynamics.

Main Results:

• Identified 227 SAH-associated PTM genes, with 12 showing causal links.
• ZRANB1 and ATG7 selected as key PTM biomarkers.
• Developed a diagnostic model with AUC=0.833 for SAH risk prediction (20%-90%).
• ZRANB1 and ATG7 levels were significantly altered in SAH patients.
• Tretinoin predicted as a therapeutic candidate with favorable binding affinities for ATG7.

Conclusions:

• Established ATG7-ZRANB1 as a novel biomarker combination for SAH prediction.
• Identified Tretinoin as a promising therapeutic candidate for SAH.
• Demonstrated the potential of PTM-based precision medicine in SAH treatment.