Polygenic Risk, Rare Variants, and Family History: Independent and Additive Effects on Coronary Heart Disease
Authors' conclusion
Incorporating PRSCHD into the PCE improves risk prediction for CHD, especially at younger ages. The associations of PRSCHD, FH, and FamHx with CHD were independent and additive.
Study context
- Population
- UK Biobank participants with genotype datawith genotype data
- Participants
- 323,373 participants
- Exposure
- Pooled cohort equations (PCE) plus polygenic risk score (PRS) for coronary heart disease (CHD) vs PCE alone
- Outcome
- Incident CHD (MI, coronary revascularization or CV death); predictive utility by AUC and NRI
- Follow-up
- 10 years
Main finding
As reported in the abstract
AUC for incident CHD
PCE
0.759
AUC · 95% CI 0.755–0.763
PCE + PRSCHD
0.773
AUC · 95% CI 0.769–0.777
Observational data: associations, not effects.
Further findings
Events
| Outcome | PRSP95 | FH | FamHx |
|---|---|---|---|
| Independent and additive risk of PRSP95, FH and FamHx (exome-sequenced subset, n = 199,997) | 10,000 | 673 | 46,163 |
AUC and net reclassification improvement (NRI) by age
- AUC and NRIEvent for PRSCHD higher before age 55 years
Independent and additive risk of PRSP95, familial hypercholesterolemia (FH) and FamHx (exome-sequenced subset, n = 199,997)
- CHD risk with PRSP95 independent of FH and FamHx
- Risks of combinations of PRSCHD, FH and FamHx additive; estimates obtainable by multiplying risk from each factor
Original publication
Polygenic Risk, Rare Variants, and Family History: Independent and Additive Effects on Coronary Heart Disease. JACC Adv. Published 26 August 2023. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →