Valvular & structural heart diseaseResearch article
Distinct Genetic Risk Profile in Aortic Stenosis Compared With Coronary Artery Disease
- Genome-wide association study
- adjusted for coronary artery disease (CAD)
- Mendelian randomization
- replication in 2 independent cohorts
- multicentre
- Data analyzed October 2022 to July 2023
Authors' conclusion
This GWAS adjusted for CAD found a distinct genetic risk profile for AS at the single-marker and polygenic level.
Study context
- Population
- Participants of European ancestry from EGAS, UK Biobank, Estonian Biobank and FinnGen with information on comorbid CAD
- Participants
- 18,792 vs 434,249
- Comparison
- Aortic stenosis (AS) vs controls, adjusted for CAD
- ASn = 18,792
- Controlsn = 434,249reference
- Outcome
- Cardiovascular traits associated with AS adjusted for CAD
Main finding
As reported in the abstract
AS risk loci
17
Loci with novel and independently replicated associations (RNF114A, AFAP1, PDGFRA, ADAMTS7, HAO1)
5
Loci associated specifically with AS, not with CAD
11
Genetic correlation between AS and CAD (SE 0.05; P = 1.60 × 10-3)
0.15
Further findings
| Outcome | OR (95% CI) | P value | |
|---|---|---|---|
| Serum phosphate (Mendelian randomization) — AS vs Controls · AS | 1.20 (1.11–1.31) | P = 1.27 × 10-5 | |
| Serum phosphate (Mendelian randomization) — CAD vs Controls · CAD | 0.97 (0.94–1.00) | P = 0.04 | |
| 0.512Odds ratio (log scale) |
BP, BMI and cholesterol metabolism (Mendelian randomization)
- Substantially lesser associations with AS compared with CAD
Original publication
Distinct Genetic Risk Profile in Aortic Stenosis Compared With Coronary Artery Disease. JAMA Cardiol. Published 1 February 2025. doi:10.1001/jamacardio.2024.3738
Summarised from the published abstract; every number is checked against it