Unbiased Discovery of Genetic Determinants of Resilience to Coronary Artery Disease (CAD): Insights From PROMISE and CATHGEN
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.
Methodological detailsunbiased, discovery and validation cohorts
- Unbiased
- Discovery and validation cohorts
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: Insights From PROMISE and CATHGEN. JACC Adv. Published 18 March 2026. doi:10.
Summarised from the published abstract; every number is checked against it