A higher polygenic score for peripheral artery disease is associated with younger age at surgery among patients undergoing revascularization

We examined whether polygenic risk for peripheral artery disease (PAD) is associated with severity among patients undergoing lower extremity revascularization at Yale New Haven Hospital. Patients were classified into European (EUR) and non-European (non-EUR) ancestry groups. Associations between the 19-variant polygenic score (PGS) and nine severity indicators were evaluated using linear and Cox regression models stratified by ancestry, followed by meta-analysis. Significant findings (p < 0.05) were assessed for replication in the UK Biobank (UKB). After quality control, 68 EUR and 59 non-EUR patients were included. In EUR patients, higher PGS was associated with increased risk for stroke (HR = 2.43, 95% CI 1.06-5.57). Meta-analysis revealed a significant association between higher PGS and younger age at surgery ({beta} = -2.90, SE = 1.28), which was replicated in the UKB ({beta} = -0.58, SE = 0.15). These results suggest genetic risk contributes to PAD severity.