Specifically, genetically predicted circulating levels of glial cell line-derived neurotrophic factor (GDNF) (OR = 1.12; 95% CI: 1.05–1.19; P = 2.72 × 10-4) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (OR = 0.93; 95% CI: 0.91–0.99; P = 1.00 × 10-2) exerted causal effects on CRC risk. Here, GDNF is linked to colorectal carcinoma.