ORIGINAL RESEARCH article
Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1413183
New perspectives on the pathogenic factors of abdominal aortic aneurysm from a multi omics standpoint: A bidirectional and after-meta Mendelian Randomization Analysis
Provisionally accepted
- 1West China Hospital, Sichuan University, Chengdu, China
- 2West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
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Abstract Objective: The objective was to elucidate the immune-metabolic mechanisms underlying abdominal aortic aneurysm formation, focusing on the causal relationships between abdominal aortic aneurysm and phenotypes including immune cells, metabolites, immune factors, and gut microbiota. Methods: A two-sample bidirectional Mendelian randomization analysis was conducted, leveraging data from large-scale Genome-Wide Association Studies and integrating findings across the mentioned phenotypes. Instrumental variables for MR analysis were selected based on stringent criteria to ensure the reliability of causal inference. The stability, heterogeneity, and pleiotropy of the results were verified using the multivariate sensitivity analysis. Results: Our analysis identified significant causal associations between AAA and various phenotypes. Notably, CX3CR1 on CD14+ CD16- monocytes demonstrated a protective effect against abdominal aortic aneurysm (Odds Ratio (OR) =0.915, 95% confidence interval (CI): 0.864 to 0.967, P=0.001). In contrast, elevated levels of Naive CD4+ T cell %T cell were associated with increased risk (OR=1.063, 95% CI: 1.016 to 1.109, P=0.008). Metabolite oleate/vaccenate (18:1) levels were positively associated with abdominal aortic aneurysm risk (OR=1.078, 95% CI: 1.028 to 1.127, P=0.002), whereas dTDP-L-rhamnose biosynthesis pathway abundance showed a protective association (OR=0.683, 95% CI: 0.597 to 0.769, P<0.001). Conclusion: This study reveals a complex impact of multi-omics in abdominal aortic aneurysm pathogenesis, highlighting specific phenotypes with significant causal relationships. These insights into the immune-metabolic mechanisms of abdominal aortic aneurysm formation provide a foundation for future research into targeted interventions for prevention and treatment.
Keywords: Abdominal Aortic Aneurysm, Mendelian randomization, Immunemetabolic mechanisms, Multi-omics study AAA: Abdominal Aortic Aneurysm, MR: Mendelian Randomization, GWAS: Genome-wide Association Studies, IVs: Instrumental Variables, CLSA: Canadian Longitudinal Study on Aging
Received: 06 Apr 2024; Accepted: 15 Jul 2025.
Copyright: © 2025 Teng, Zhu, Lu, Tang and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zheyu Chen, West China Hospital, Sichuan University, Chengdu, China
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