Coronary disease & ACSResearch article
Polygenic Risk in Families With Spontaneous Coronary Artery Dissection
- Genetic association study
Authors' conclusion
Extreme aggregation of common genetic risk appears to play a significant role in familial clustering of SCAD as well as in sporadic case predisposition, although further study is required.
Study context
- Population
- Families with spontaneous coronary artery dissection (SCAD), individuals with sporadic SCAD and healthy controls; recruited 2017–202113 families
- Participants
- 27 / 12 / 173 / 1,127
- Comparison
- Familial SCAD, sporadic SCAD and unaffected family members vs healthy controls (SCAD polygenic risk score (PRS))
- Affected family membersn = 27
- Unaffected family membersn = 12
- Sporadic SCADn = 173
- Healthy controlsn = 1,127reference
- Outcome
- Disease status (familial SCAD, sporadic SCAD or healthy control) associated with PRS (7 single-nucleotide variants)
Main finding
As reported in the abstract
Association with SCAD PRS (OR per 1-SD increase in PRS)
Each group vs healthy controlsOdds ratio (95% CI)P value
Affected family members
2.14(1.78–2.50)
adjusted P = 1.96 × 10-4Sporadic SCAD
1.63(1.37–1.89)
adjusted P = 5.69 × 10-4Unaffected family members
1.03(0.46–1.61)
adjusted P = .91Further findings
| Outcome | OR (95% CI) | P value | |
|---|---|---|---|
| Overrepresentation in top quintile of control PRS distribution — Affected family members vs Healthy controls | 3.70 (2.93–4.47) | adjusted P = .001 | |
| Overrepresentation in top quintile of control PRS distribution — Sporadic SCAD vs Healthy controls | 2.51 (1.98–3.04) | adjusted P = .001 | |
| 0.20.5125Odds ratio (log scale) |
Rare deleterious variants in connective tissue disorders (CTD)-associated genes
- Affected individuals within a family did not share any rare deleterious variants in CTD-associated genes
Original publication
Polygenic Risk in Families With Spontaneous Coronary Artery Dissection. JAMA Cardiol. Published 1 March 2024. doi:10.1001/jamacardio.2023.5194
Summarised from the published abstract; every number is checked against it