Genetically instrumented LDL-cholesterol lowering and multiple disease outcomes: A Mendelian randomization phenome-wide association study in the UK Biobank.

ABSTRACT:

Aims

Lipid-lowering medications are widely used to control blood cholesterol levels and manage a range of cardiovascular and lipid disorders. We aimed to explore the possible associations between LDL lowering and multiple disease outcomes or biomarkers.

Methods

We performed a Mendelian randomization phenome-wide association study (MR-PheWAS) in 337 475 UK Biobank participants to test for associations between four proposed LDL-C-lowering genetic risk scores (PCSK9, HMGCR, NPC1L1 and LDLR) and 1135 disease outcomes, with follow-up MR analyses in 52 serum, urine, imaging and clinical biomarkers. We used inverse-variance weighted MR in the main analyses and complementary MR methods (weighted median, weighted mode, MR-Egger and MR-PRESSO) as sensitivity analyses. We accounted for

SUBMITTER: Pham K 

PROVIDER: S-EPMC10952153 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature