PAD-associated Genetic Variants are More Strongly Associated with Surgical Intervention than Premature Onset

This study explored the association between 19 peripheral artery disease (PAD)-associated variants and PAD severity. We classified PAD cases into 4 groups with increasing levels of severity based on age of PAD diagnosis and surgical status. Genetic association analysis for PAD severity and markers was conducted using REGENIE, and a 19-variant polygenic risk score (PRS) was developed to further evaluate the associations with severity subtypes. Two SNPs (rs4722172 and rs505922) showed stronger odds ratios (ORs) with more severe subtypes. The 19-variant PRS was significantly higher in surgical compared to non-surgical groups (OR = 1.14, 95% CI: 1.08, 1.20; p-value = 5.85 × 10^-7) while no significant difference for non-premature and premature PAD (OR = 0.98, 95% CI: 0.9, 1.07, p-value = 0.64). This same pattern was observed in the subjects from Generations dataset. Our findings demonstrate that PAD-associated SNPs may also be associated with PAD severity as assessed by surgical intervention and age of onset (or diagnosis).