SMR analysis also showed consistent causal associations between genetically predicted CYP21A2, DENND5B and increased risk of DM-PAD: CYP21A2 (OR: 1.49; 95%CI: 1.33–1.66; pSMRFDR = 8.22 × 10–9), DENND5B (OR: 1.26; 95%CI: 1.21–1.40; pSMRFDR = 2.31 × 10–2), while C4A was associated with decreased risk of DM-PAD: C4A (OR: 0.73; 95%CI: 0.67–0.79; pSMRFDR = 3.54 × 10–9; Figure 3B). This evidence concerns the gene DENND5B and peripheral arterial disease.