Coronary disease & ACSDiagnostic or prognostic study
Unbiased Discovery of Genetic Determinants of Resilience to Coronary Artery Disease (CAD)
- genome-wide association analyses
- unbiased
- discovery and validation cohorts
Authors' conclusion
Resilience to CAD-defined as the absence of coronary atherosclerosis despite high clinical and polygenic risk-is present in both lower- (PROMISE) and higher-risk (CATHGEN) cohorts and is linked to protective variants in metabolic and vascular pathways. This unbiased, proof-of-concept approach reveals biologically plausible targets for replication and mechanistic studies in larger imaging-based genetics cohorts.
Study context
- Population
- Individuals with high clinical and polygenic risk of CAD, with well-defined coronary anatomy, compared with patients with obstructive CAD2 genotyped cohorts · PROMISE (discovery cohort: coronary computed tomography angiography) 605 · CATHGEN (validation cohort: invasive angiography) 3,236
- Comparison
- Resilient individuals were compared to patients with obstructive CAD (oCAD) (stenosis ≥70%) using genome-wide association analyses at variant, gene, and pathway levels.
Performance
As reported in the abstract
Resilience and oCAD, PROMISE
Further findings
Resilience and oCAD, CATHGEN
- Resilience and oCAD, CATHGEN: CATHGEN n = 3,236
Clinical risk factors and polygenic risk scores
- Similar between resilient and oCAD patients in both cohorts
Variant- and gene-level analyses
- No genome-wide significant signals
Pathway-level analyses
- 4 resilience-associated pathways in PROMISE that replicated in CATHGEN: adipocytokine signaling, fatty acid metabolism, fatty acid degradation, and vascular smooth muscle contraction
Original publication
Unbiased Discovery of Genetic Determinants of Resilience to CAD. JACC Adv. Published 18 March 2026. doi:10.1016/j.jacadv.2026.102665
Summarised from the published abstract; every number is checked against it