Specifically, inverse-variance weighted (IVW) and Wald ratio analysis results revealed that a causal association between genetically predicted CYP21A2, and DENND5B and higher risk of DM-PAD were observed: CYP21A2 (OR: 1.33; 95%CI: 1.19–1.50; IVWFDR = 8.41 × 10–6), DENND5B (OR: 1.17; 95%CI: 1.09–1.26; IVWFDR = 1.57 × 10–4), C4A and lower risk of DM-PAD were detected: C4A (OR: 0.74; 95%CI: 0.68–0.80; Wald ratio FDR = 3.62 × 10–12; Figure 3B). This evidence concerns the gene CYP21A2 and peripheral arterial disease.