ArticleEuropean heart journal2021
Metabolic profiling of angiopoietin-like protein 3 and 4 inhibition: a drug-target Mendelian randomization analysis.
Article in European heart journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 2 syntheses or guidelines pooled it, 108 citations in OpenAlex.
- The landscape of the methodology in drug repurposing using human genomic data: a systematic review.Briefings in bioinformatics · 2024Pooled it
- Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease.Nature communications · 2022Pooled it
- Drug targets for lipid modification and risk of type 2 diabetes: a cis-Mendelian randomization study.Cardiovascular diabetology · 2026Article
- Assessing long-term pleiotropic effects of potential novel triglyceride-lowering medications using variants identified by Mendelian randomization.medRxiv : the preprint server for health sciences · 2025Article
- Statins Regulate Stem Cell Growth Factor-β to Balance Osteogenesis and Adipogenesis in Mesenchymal Stem Cells, Endowing Anti-Osteonecrosis Effects.Journal of cellular and molecular medicine · 2025Article
- Article
- A genetic map of human metabolism across the allele frequency spectrum.Nature genetics · 2025Article
- Genetic insights into causal effects of lipids and lipid-modifying targets on calcific aortic valve stenosis: a Mendelian randomized study.Scientific reports · 2025Article
- Insights into Causal Associations of Lipid Traits and Lipid-modifying Drug Targets with Uric Acid and Risk of Gout.Phenomics (Cham, Switzerland) · 2025Article
- Optimizing treatment of cardiovascular risk factors in cerebral small vessel disease using genetics.Brain : a journal of neurology · 2025Article
- scPrediXcan integrates deep learning methods and single-cell data into a cell-type-specific transcriptome-wide association study framework.Cell genomics · 2025Article
- scPrediXcan integrates advances in deep learning and single-cell data into a powerful cell-type-specific transcriptome-wide association study framework.bioRxiv : the preprint server for biology · 2025Article
- Insights Into Causal Effects of Genetically Proxied Lipids and Lipid-Modifying Drug Targets on Cardiometabolic Diseases.Journal of the American Heart Association · 2025Article
- ANGPTL4-the Link Binding Lipid Metabolism and Inflammation.Current medicinal chemistry · 2025Review
- Antibody-Based Therapeutics for Hypercholesterolemia.Biologics : targets & therapy · 2025Review
- The Causal Mechanism Between the Dipeptidyl Peptidase-4, Heart Failure, and Other Cardiovascular Diseases: A Mendelian Randomization and Mediation Study.International journal of endocrinology · 2025Article
- Impact of Remnant Cholesterol on Cardiovascular Risk in Diabetes.Current diabetes reports · 2024Review
- Magnesium Depletion Score and Metabolic Syndrome in US Adults: Analysis of NHANES 2003 to 2018.The Journal of clinical endocrinology and metabolism · 2024Article
- Causal inference in health and disease: a review of the principles and applications of Mendelian randomization.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Review
- Drug-target Mendelian randomisation applied to metabolic dysfunction-associated steatotic liver disease: opportunities and challenges.eGastroenterology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 10 institutions in 4 countries.
Funding
Abstract
aimsAngiopoietin-like protein 3 (ANGPTL3) and 4 (ANGPTL4) inhibit lipoprotein lipase (LPL) and represent emerging drug targets to lower circulating triglycerides and reduce cardiovascular risk. To investigate the molecular effects of genetic mimicry of ANGPTL3 and ANGPTL4 inhibition and compare them to the effects of genetic mimicry of LPL enhancement. METHODS AND
resultsAssociations of genetic variants in ANGPTL3 (rs11207977-T), ANGPTL4 (rs116843064-A), and LPL (rs115849089-A) with an extensive serum lipid and metabolite profile (208 measures) were characterized in six cohorts of up to 61 240 participants. Genetic associations with anthropometric measures, glucose-insulin metabolism, blood pressure, markers of kidney function, and cardiometabolic endpoints via genome-wide summary data were also explored. ANGPTL4 rs116843064-A and LPL rs115849089-A displayed a strikingly similar pattern of associations across the lipoprotein and lipid measures. However, the corresponding associations with ANGPTL3 rs11207977-T differed, including those for low-density lipoprotein and high-density lipoprotein particle concentrations and compositions. All three genotypes associated with lower concentrations of an inflammatory biomarker glycoprotein acetyls and genetic mimicry of ANGPTL3 inhibition and LPL enhancement were also associated with lower C-reactive protein. Genetic mimicry of ANGPTL4 inhibition and LPL enhancement were associated with a lower waist-to-hip ratio, improved insulin-glucose metabolism, and lower risk of coronary heart disease and type 2 diabetes, whilst genetic mimicry of ANGPTL3 was associated with improved kidney function.
conclusionsGenetic mimicry of ANGPTL4 inhibition and LPL enhancement have very similar systemic metabolic effects, whereas genetic mimicry of ANGPTL3 inhibition showed differing metabolic effects, suggesting potential involvement of pathways independent of LPL. Genetic mimicry of ANGPTL4 inhibition and LPL enhancement were associated with a lower risk of coronary heart disease and type 2 diabetes. These findings reinforce evidence that enhancing LPL activity (either directly or via upstream effects) through pharmacological approaches is likely to yield benefits to human health.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.