ArticleNature communications2014
A rare variant in APOC3 is associated with plasma triglyceride and VLDL levels in Europeans.
Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 46 papers, 2 of them syntheses that pooled it.
What it found
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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.
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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.
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Who cites it
46 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Very low-depth sequencing in a founder population identifies a cardioprotective APOC3 signal missed by genome-wide imputation.Human molecular genetics · 2016Pooled it
- Five endometrial cancer risk loci identified through genome-wide association analysis.Nature genetics · 2016Pooled it
- Postprandial metabolism of apolipoproteins B48, B100, C-III, and E in humans with APOC3 loss-of-function mutations.JCI insight · 2022Trial
- Gene-based therapies for steatotic liver disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Trans-ancestral rare variant association study with machine learning-based phenotyping for metabolic dysfunction-associated steatotic liver disease.Genome biology · 2025Article
- Multifaceted Role of Apolipoprotein C3 in Cardiovascular Disease Risk and Metabolic Disorder in Diabetes.International journal of molecular sciences · 2024Review
- Article
- Drug-target Mendelian randomization analysis supports lowering plasma ANGPTL3, ANGPTL4, and APOC3 levels as strategies for reducing cardiovascular disease risk.European heart journal open · 2024Article
- Article
- Current Data and New Insights into the Genetic Factors of Atherogenic Dyslipidemia Associated with Metabolic Syndrome.Diagnostics (Basel, Switzerland) · 2023Review
- Outcome Monitoring After Cardiac Surgery (OMACS): a single-centre prospective cohort study of cardiac surgery patients.BMJ open · 2022Article
- Etiologic Puzzle of Coronary Artery Disease: How Important Is Genetic Component?Life (Basel, Switzerland) · 2022Review
- The role of lipid traits in mediating the effect of body mass index on serum urate.Frontiers in endocrinology · 2022Observational
- CRISPR/Cas9-mediated knockout of APOC3 stabilizes plasma lipids and inhibits atherosclerosis in rabbits.Lipids in health and disease · 2021Article
- Genetically-engineered hamster models: applications and perspective in dyslipidemia and atherosclerosis-related cardiovascular disease.Medical review (2021) · 2021Article
- Metabolic characterisation of disturbances in the APOC3/triglyceride-rich lipoprotein pathway through sample-based recall by genotype.Metabolomics : Official journal of the Metabolomic Society · 2020Article
- Integrating DNA sequencing and transcriptomic data for association analyses of low-frequency variants and lipid traits.Human molecular genetics · 2020Article
- An adaptive test for meta-analysis of rare variant association studies.Genetic epidemiology · 2020Article
- Article
- Global genetic diversity of human apolipoproteins and effects on cardiovascular disease risk.Journal of lipid research · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
35 authors.
Funding
Abstract
The analysis of rich catalogues of genetic variation from population-based sequencing provides an opportunity to screen for functional effects. Here we report a rare variant in APOC3 (rs138326449-A, minor allele frequency ~0.25% (UK)) associated with plasma triglyceride (TG) levels (-1.43 s.d. (s.e.=0.27 per minor allele (P-value=8.0 × 10(-8))) discovered in 3,202 individuals with low read-depth, whole-genome sequence. We replicate this in 12,831 participants from five additional samples of Northern and Southern European origin (-1.0 s.d. (s.e.=0.173), P-value=7.32 × 10(-9)). This is consistent with an effect between 0.5 and 1.5 mmol l(-1) dependent on population. We show that a single predicted splice donor variant is responsible for association signals and is independent of known common variants. Analyses suggest an independent relationship between rs138326449 and high-density lipoprotein (HDL) levels. This represents one of the first examples of a rare, large effect variant identified from whole-genome sequencing at a population scale.
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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.