Biological age and genetic risk with incident peripheral arterial disease in UK Biobank
In 403,780 UK Biobank participants free of peripheral arterial disease at baseline, accelerated biological aging was associated with higher risk of incident PAD, and the highest risk appeared in those with both accelerated aging and high genetic risk. [1]
Automatic summary · not editorially reviewed
The key findings
The prospective UK Biobank study included 403,780 participants free of peripheral arterial disease at baseline and estimated biological age from routine clinical biomarkers with the Klemera-Doubal method and PhenoAge. [1]
Accelerated biological aging was associated with increased risk of incident PAD, with hazard ratios of 1.21 for the Klemera-Doubal residual and 1.34 for the PhenoAge residual. [1]
Participants with both accelerated biological aging and high genetic risk had the greatest PAD risk, and a significant additive interaction was observed for PhenoAge-measured aging. [1]
The source at a glance
- Study type / format
- Prospective cohort study (abstract)
- Population / context
- 403,780 UK Biobank participants free of peripheral arterial disease at baseline
- Summary based on
- Study abstract
- Original publication
- June 25, 2026
Biological age measures in PAD-free UK Biobank adults
This prospective UK Biobank cohort study asked whether biological aging and genetic susceptibility relate to the risk of developing peripheral arterial disease (PAD), in which atherosclerosis narrows or blocks peripheral arteries and reduces blood supply to the limbs. It included 403,780 participants who were free of PAD at baseline. Biological age was estimated from routine clinical biomarkers using two algorithms, the Klemera-Doubal method and PhenoAge. Biological age acceleration was defined as the residual from regressing biological age on chronological age. A polygenic risk score was built to assess genetic predisposition to PAD.
Supporting source [1]
Higher PAD risk with accelerated aging and high genetic risk
In models adjusted for demographic, socioeconomic, lifestyle and clinical factors, accelerated biological aging was significantly associated with increased risk of incident PAD: hazard ratio 1.21 (95% confidence interval 1.18–1.24) by the Klemera-Doubal residual and 1.34 (1.31–1.37) by the PhenoAge residual. In joint analysis, participants with both accelerated biological aging and high genetic risk had the greatest risk (Klemera-Doubal: HR 2.07, 95% CI 1.83–2.34; PhenoAge: HR 6.14, 95% CI 5.30–7.12). A significant additive interaction was observed between high genetic risk and accelerated aging measured by PhenoAge.
Supporting source [1]
Abstract-only scope of the UK Biobank PAD analysis
The authors conclude that accelerated biological aging was independently and jointly associated with incident PAD and suggest that biological aging metrics could be integrated into PAD risk assessment. These are associations from an observational cohort, not evidence that accelerated aging causes PAD. The abstract does not report follow-up duration, the number of PAD events, or how genetic risk categories were defined. Only the abstract was reviewed; the full text was not reviewed.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. This is an observational cohort, so the reported associations do not establish causation. Follow-up duration, number of PAD events and definitions of genetic risk categories are not reported in the abstract.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Zhang W, Qiu P, Li C, Wang R. · europepmc.org · June 25, 2026