Aortic & peripheral vascular diseaseCohort study
Polygenic Prediction of Peripheral Artery Disease and Major Adverse Limb Events
- Longitudinal cohort study
- multiancestry
- 3 populations
- Data analyzed July 2023 to February 2025
Authors' conclusion
This cohort study develops a new PRS that stratifies risk of PAD and adverse limb outcomes.
Study context
- Population
- Individuals with genotyping and electronic health record data in UK Biobank (2006–2021), All of Us (2018–2022) and Mass General Brigham Biobank (MGBB) (2010–2023)3 cohorts: UK Biobank 400,533, All of Us (AoU) 218,500, MGBB 32,982
- Exposure
- High vs remaining PRS-PAD
- Outcome
- PAD and major adverse limb events (surrogate of major amputation and acute limb ischemia)
Main finding
As reported in the abstract
PAD (UK Biobank validation cohort)
Odds ratio (95% CI)P value
PRS-PAD per SD increase
1.63(1.60–1.68)
P < 0.001Top 20% PRS-PAD vs Remainderadjusted for clinical risk factors
1.68(1.62–1.74)
P < 0.001Observational data: associations, not effects.
Further findings
| Outcome | HR (95% CI) | P value | |
|---|---|---|---|
| Incident major adverse limb events among prevalent PAD, high PRS-PAD — High PRS-PAD vs Remainder · UK Biobank | 1.75 (1.18–2.57) | P = 0.005 | |
| Incident major adverse limb events among prevalent PAD, high PRS-PAD — High PRS-PAD vs Remainder · MGBB | 1.56 (1.06–2.30) | P = 0.02 | |
| Incident major adverse limb events among prevalent PAD, high PRS-PAD — High PRS-PAD vs Remainder · AoU | 1.57 (1.06–2.33) | P = 0.03 | |
| 0.20.5125Hazard ratio (log scale) |
Incident peripheral artery disease (PAD) discrimination (C statistic)
- PRS-PAD
- 0.761
- Diabetes
- 0.760
- Smoking
- 0.765
High PRS-PAD (top 20%) among PAD cases without diabetes, smoking or CKD (n = 3645)
- 1097 individuals
- 30.1%
Original publication
Polygenic Prediction of Peripheral Artery Disease and Major Adverse Limb Events. JAMA Cardiol. Published 1 August 2025. doi:10.1001/jamacardio.2025.1182
Summarised from the published abstract; every number is checked against it