SynthesisLancet (London, England)2012
Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study.
Synthesis in Lancet (London, England), 2012. 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 1,085 papers, 12 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
1,085 citing papers in PubMed, 12 syntheses or guidelines pooled it, 118 citations in OpenAlex.
- Context-Dependent Associations of theInternational journal of molecular sciences · 2026Pooled it
- Causal association between lipoproteins and risk of coronary artery disease-a systematic review and meta-analysis of Mendelian randomization studies.Clinical research in cardiology : official journal of the German Cardiac Society · 2026Pooled it
- Genome-wide gene-sleep interaction study identifies novel lipid loci in 732,564 participants.Atherosclerosis · 2026Pooled it
- Efficacy and safety of PCSK-9 inhibitors in patients with acute coronary syndrome: a systematic review and network meta-analysis.BMC cardiovascular disorders · 2025 · on this mapPooled it
- High-density lipoprotein particles are associated with the risk of mortality from all-causes and cardiovascular diseases (CVDs) in patients with CVD: a systematic review and meta-analysis study.Lipids in health and disease · 2025Pooled it
- Apolipoproteins, lipids, lipid-lowering drugs and risk of amyotrophic lateral sclerosis and frontotemporal dementia: a meta-analysis and Mendelian randomisation study.Journal of neurology · 2024Pooled it
- Mendelian randomization studies on coronary artery disease: a systematic review and meta-analysis.Systematic reviews · 2024Pooled it
- Association of LDL-cholesterol subfractions with cardiovascular disorders: a systematic review.BMC cardiovascular disorders · 2023Pooled it
- Effect of Isoenergetic Substitution of Cheese with Other Dairy Products on Blood Lipid Markers in the Fasted and Postprandial State: An Updated and Extended Systematic Review and Meta-Analysis of Randomized Controlled Trials in Adults.Advances in nutrition (Bethesda, Md.) · 2023Pooled it
- Vegetarian or vegan diets and blood lipids: a meta-analysis of randomized trials.European heart journal · 2023Pooled it
- HDL-cholesterol concentration and its association with coronary artery calcification: a systematic review and meta-analysis.Lipids in health and disease · 2023Pooled it
- Long-term cardiometabolic health in people born after assisted reproductive technology: a multi-cohort analysis.European heart journal · 2023Pooled it
- Obicetrapib in patients with heterozygous familial hypercholesterolemia: the BROOKLYN randomized clinical trial.Nature medicine · 2026Trial
- Effectiveness of treat-to-target cholesterol-lowering interventions on cardiovascular disease and all-cause mortality risk in the community-dwelling population: a target trial emulation.Nature communications · 2024Trial
- Trial
- Letter to the editor: reflections on "predictive value of high-density lipoprotein cholesterol and the cardio-ankle vascular index on cardiovascular outcomes in subjects with cardiovascular risks: the COUPLING study".Hypertension research : official journal of the Japanese Society of Hypertension · 2026Article
- Profiling Cardiovascular Disease-Associated Changes in the Composition of High-Density Lipoprotein Particles.Cardiovascular drugs and therapy · 2026Review
- Alcohol-aware risk stratification and subtype-specific care pathways across metabolic dysfunction-associated steatotic liver disease, metabolic dysfunction and alcohol-associated liver disease, and alcohol-associated liver disease.Clinical and molecular hepatology · 2026Review
- Interpreting Lower HDL Cholesterol in Plant-Based Diets: Mechanisms and Clinical Implications.Advances in nutrition (Bethesda, Md.) · 2026Review
- An Integrated Multi-omics Single Cell Atlas of the Human RPE and Choroid.bioRxiv : the preprint server for biology · 2026Article
1,025 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
126 authors at 1 institution in 1 country.
Funding
Abstract
backgroundHigh plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes, mendelian randomisation can be used to test the hypothesis that the association of a plasma biomarker with disease is causal.
methodsWe performed two mendelian randomisation analyses. First, we used as an instrument a single nucleotide polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser) and tested this SNP in 20 studies (20,913 myocardial infarction cases, 95,407 controls). Second, we used as an instrument a genetic score consisting of 14 common SNPs that exclusively associate with HDL cholesterol and tested this score in up to 12,482 cases of myocardial infarction and 41,331 controls. As a positive control, we also tested a genetic score of 13 common SNPs exclusively associated with LDL cholesterol.
findingsCarriers of the LIPG 396Ser allele (2·6% frequency) had higher HDL cholesterol (0·14 mmol/L higher, p=8×10(-13)) but similar levels of other lipid and non-lipid risk factors for myocardial infarction compared with non-carriers. This difference in HDL cholesterol is expected to decrease risk of myocardial infarction by 13% (odds ratio [OR] 0·87, 95% CI 0·84-0·91). However, we noted that the 396Ser allele was not associated with risk of myocardial infarction (OR 0·99, 95% CI 0·88-1·11, p=0·85). From observational epidemiology, an increase of 1 SD in HDL cholesterol was associated with reduced risk of myocardial infarction (OR 0·62, 95% CI 0·58-0·66). However, a 1 SD increase in HDL cholesterol due to genetic score was not associated with risk of myocardial infarction (OR 0·93, 95% CI 0·68-1·26, p=0·63). For LDL cholesterol, the estimate from observational epidemiology (a 1 SD increase in LDL cholesterol associated with OR 1·54, 95% CI 1·45-1·63) was concordant with that from genetic score (OR 2·13, 95% CI 1·69-2·69, p=2×10(-10)).
interpretationSome genetic mechanisms that raise plasma HDL cholesterol do not seem to lower risk of myocardial infarction. These data challenge the concept that raising of plasma HDL cholesterol will uniformly translate into reductions in risk of myocardial infarction.
fundingUS National Institutes of Health, The Wellcome Trust, European Union, British Heart Foundation, and the German Federal Ministry of Education and Research.
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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.