The results indicate that only LDL-C (multivariable IVW, OR:1.65; 95%CI:1.15–2.36, FDR = 0.025) and BMI (multivariable IVW, OR:1.82; 95%CI:1.33–2.47, FDR < 0.001) have a causal association with DM-PAD, while DENND5B gene, does not appear to be directly involved in the development of DM-PAD (multivariable IVW, OR:1.08; 95%CI: 0.74–1.58, FDR = 0.772; Figure 4D). This evidence concerns the gene DENND5B and peripheral arterial disease.