Multi-biobank Mendelian randomization analyses identify opposing pathways in plasma low-density lipoprotein-cholesterol lowering and gallstone disease.

ABSTRACT: Plasma low-density lipoprotein (LDL)-cholesterol is positively associated with coronary artery disease risk while biliary cholesterol promotes gallstone formation. Different plasma LDL-cholesterol lowering pathways may have distinct effects on biliary cholesterol and thereby gallstone disease risk. We conducted a Mendelian randomization (MR) study using data from the UK Biobank (30,547 gallstone disease cases/336,742 controls), FinnGen (34,461 cases/301,383 controls) and Biobank Japan (9,305 cases/168,253 controls). We first performed drug-target MR analyses substantiated by colocalization to investigate the effects of plasma LDL-cholesterol lowering therapies on gallstone disease risk. We then performed clustered MR analyses and pathway analyses to identify distinct mechanisms underlying

SUBMITTER: Yang G 

PROVIDER: S-EPMC11410903 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature