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Proteome-Wide Mendelian Randomization Reveals Biomarkers for Abdominal Aortic Aneurysm

J Invest Surg. 2026 Dec;39(1):2560332. doi: 10.1080/08941939.2025.2560332. Epub 2026 Jan 8.

ABSTRACT

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.

PMID:41503834 | DOI:10.1080/08941939.2025.2560332

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