Specifically, genetically predicted higher levels of CROT (OR = 1.08, 95% CI = 1.04–1.12) were positively associated with an increased risk of cholelithiasis, while higher levels of SPHK2 (OR = 0.75, 95% CI = 0.65–0.86) were associated with a decreased risk of cholelithiasis. This evidence concerns the gene SPHK2 and cholelithiasis.