ArticleBritish journal of clinical pharmacology2023
Genetically instrumented LDL-cholesterol lowering and multiple disease outcomes: A Mendelian randomization phenome-wide association study in the UK Biobank.
Article in British journal of clinical pharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Genome-wide gene-environment interaction study uncovers 162 vitamin D status variants using a precise ambient UVB measure.Nature communications · 2025Article
- Associations of Circulating Biomarkers with Disease Risks: A Two-Sample Mendelian Randomization Study.International journal of molecular sciences · 2024Article
- Associations of Circulating Biomarkers with Disease Risks: a Two-Sample Mendelian Randomization Study.medRxiv : the preprint server for health sciences · 2024Article
- Causal relationships involving brain imaging-derived phenotypes based on UKB imaging cohort: a review of Mendelian randomization studies.Frontiers in neuroscience · 2024Review
- Genetically instrumented LDL-cholesterol lowering and multiple disease outcomes: A Mendelian randomization phenome-wide association study in the UK Biobank.British journal of clinical pharmacology · 2023Article
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Authors and funding
4 authors.
Funding
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Abstract
aimsLipid-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.
methodsWe 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 multiple testing with false discovery rate correction (P < 2.0 × 10
resultsWe found evidence for an association between genetically instrumented LDL lowering and 10 distinct disease outcomes, suggesting potential causality. All genetic instruments were associated with hyperlipidaemias and cardiovascular diseases in the expected directions. Biomarker analyses supported an effect of LDL-C lowering through PCSK9 on lung function (FEV [beta per 1 mg/dL lower LDL-C -1.49, 95% CI -2.21, -0.78]; FVC [-1.42, 95% CI -2.29, -0.54]) and through HMGCR on hippocampal volume (beta per 1 mg/dL lower LDL-C 6.09, 95% CI 1.74, 10.44).
conclusionsWe found genetic evidence to support both positive and negative effects of LDL-C lowering through all four LDL-C-lowering pathways. Future studies should further explore the effects of LDL-C lowering on lung function and changes in brain volume.
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