Aortic & peripheral vascular diseaseDiagnostic or prognostic study
Epigenome-Wide Association Study of Abdominal Aortic Aneurysm Identifies Central Role for Inflammatory Pathways
- Epigenome-wide association study with Mendelian randomization
- stratified analyses by population group and smoking status
- network Mendelian randomization
- external validation in 2 studies
Authors' conclusion
This study identified putative causal DNA methylation markers for AAA, and multi-omics analyses implicate activator protein-1-linked inflammatory transcriptional programs, blood lipids, and multiple inflammation-related proteins as key pathways underlying methylation-associated AAA risk.
Study context
- Population
- Veterans Affairs Million Veteran Program
- Participants
- 1,324 vs 42,065
- Comparison
- Cases vs Noncases
- Casesn = 1,324
- Noncasesn = 42,065reference
- Outcome
- DNA methylation (CpG) markers associated with incident AAA
Performance
As reported in the abstract
- CpGs associated with incident abdominal aortic aneurysm (AAA)
- 1253
- CpG-AAA associations with putative causal role supported by Mendelian randomization
- 143
- CpG-gene expression pairs with strong colocalization support (incl. AGER, C2, DDR1)
- 213
- CpG-gene expression-AAA links prioritized by multi-trait colocalization
- 8
- Putative mediation pathways linking CpGs to AAA
- 135
- Mediation pathways via cardiometabolic traits
- 58
- Mediation pathways via inflammation-related traits
- 77
- Proportion of CpG-AAA associations near LDLR (cg19305903) and TRIB1 (cg14128479) mediated by blood lipid traits
- >40%
Further findings
Methylation risk score for AAA
- Strongly associated with AAA in the discovery cohort and 2 external validation cohorts, even after adjustment for clinical covariates
Original publication
Epigenome-Wide Association Study of Abdominal Aortic Aneurysm Identifies Central Role for Inflammatory Pathways. Circulation. Published 29 September 2026. doi:10.1161/circulationaha.126.079863
Summarised from the published abstract; every number is checked against it