Novel insights into causal effects of serum lipids and lipid-modifying targets on cholelithiasis
Objective Different serum lipids and lipid-modifying targets should affect the risk of cholelithiasis differently, however, whether such effects are causal is still controversial and we aimed to answer this question. Design We prospectively estimated the associations of four serum lipids with cholelithiasis in UK Biobank using the Cox proportional hazard model, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG). Furthermore, we estimated the causal associations of the genetically predicted serum lipids with cholelithiasis in Europeans using the Mendelian randomisation (MR) design. Finally, both drug-target MR and colocalisation analyses were performed to estimate the lipid-modifying targets’ effects on cholelithiasis, including HMGCR , NPC1L1 , PCSK9 , APOB, LDLR, ACLY, ANGPTL3, MTTP, PPARA, PPARD and PPARG . Results We found that serum levels of LDL-C and HDL-C were inversely associated wit