Proteome-Wide Mendelian Randomization Reveals Biomarkers for Abdominal Aortic Aneurysm

BACKGROUND: Abdominal aortic aneurysm (AAA) is a progressive vascular disorder that enlarges irreversibly and may ultimately rupture. Mendelian randomization (MR) provides a powerful approach to uncover biomarkers. We aimed to identify plasma proteins linked to AAA and evaluate their diagnostic potential. METHODS: We performed a proteome-wide MR analysis using genetic instruments for 2,940 plasma proteins from the UK Biobank Pharma Proteomics Project (UKB-PPP). Summary statistics for AAA were obtained from the Finnish R9 GWAS, comprising 4,083 cases and 420,324 controls. RESULTS: Eleven proteins showed significant causal associations with AAA risk (FDR < 0.05): seven positively and four negatively associated, highlighting their potential as diagnostic markers. CONCLUSION: This study provides the first proteome-wide MR evidence linking plasma proteins to AAA, offering candidate biomarkers for diagnosis. As a hypothesis-generating work, further experimental and clinical validation is warranted.