ArticleCirculation2024
Rare Genetic Variants in
Article in Circulation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- PRMT3-Mediated Arginine Methylation Stabilizes PCSK9 to Promote Aortic Valve Calcification.Circulation · 2026Article
- Exogenous Ganglioside GM3 Attenuates Atherosclerosis via Multi-Organ Modulation of Lipid Metabolism.Pharmaceutics · 2026Article
- The functional landscape of coding variation in the familial hypercholesterolemia geneScience (New York, N.Y.) · 2026Article
- Multiomics: the intersection of personalized nutrition in cardiometabolic diseases.Journal of translational medicine · 2026Review
- Familial Hypercholesterolemia.Methodist DeBakey cardiovascular journal · 2026Review
- Lipoprotein(a) and calcific aortic stenosis: from inherited risk marker to therapeutic target.Frontiers in medicine · 2026Review
- Shared Risk Factors and Molecular Mechanisms Between Aortic Stenosis and Atherosclerosis: A Rationale for Therapeutic Repositioning.International journal of molecular sciences · 2025Review
- Genetic insights into causal effects of lipids and lipid-modifying targets on calcific aortic valve stenosis: a Mendelian randomized study.Scientific reports · 2025Article
- Prioritization of potential drug targets for diabetic kidney disease using integrative omics data mining and causal inference.Journal of pharmaceutical analysis · 2025Article
- Lipid-lowering therapies for aortic stenosis: a drug-target Mendelian randomization study.European heart journal. Cardiovascular pharmacotherapy · 2025Article
- Prioritization of Lipid Metabolism Targets for the Diagnosis and Treatment of Cardiovascular Diseases.Research (Washington, D.C.) · 2025Article
- Optimal calorie restriction threshold: effect of FATmax exercise combined with different proportions of calorie restriction on hypercholesterolemia.Frontiers in physiology · 2025Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
backgroundDespite a proposed causal role for LDL-C (low-density lipoprotein cholesterol) in aortic stenosis (AS), randomized controlled trials of lipid-lowering therapy failed to prevent severe AS. We aimed to assess the impact on AS and peak velocity across the aortic valve conferred by lifelong alterations in LDL-C levels mediated by protein-disrupting variants in 3 clinically significant genes for LDL (low-density lipoprotein) metabolism (
methodsWe used sequencing data and electronic health records from UK Biobank (UKB) and All of Us and magnetic resonance imaging data from UKB. We identified predicted protein-disrupting variants with the Loss Of Function Transcript Effect Estimator (LOFTEE) and AlphaMissense algorithms and evaluated their associations with LDL-C and peak velocity across the aortic valve (UK Biobank), as well as diagnosed AS and aortic valve replacement (UK Biobank and All of Us).
resultsWe included 421 049 unrelated participants (5621 with AS) in UKB and 195 519 unrelated participants (1087 with AS) in All of Us. Carriers of protein-disrupting variants in
conclusionsRare genetic variants that confer lifelong higher or lower LDL-C levels are associated with substantially increased and decreased risk of AS, respectively. Early and sustained lipid-lowering therapy may slow or prevent AS development.
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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.