ArticleJACC. Basic to translational science2018
Mendelian Randomization Studies Promise to Shorten the Journey to FDA Approval.
Article in JACC. Basic to translational science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis 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.
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
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Vitamin D and Multiple Health Outcomes: An Umbrella Review of Observational Studies, Randomized Controlled Trials, and Mendelian Randomization Studies.Advances in nutrition (Bethesda, Md.) · 2022Pooled it
- Genetic and Conventional Risk Stratification Are Complementary for Primary Prevention of CAD.Methodist DeBakey cardiovascular journal · 2026Review
- Genetic Association of Lipids and Lipid-Lowering Drug Target Genes With Atopic Dermatitis: A Drug Target Mendelian Randomization Study.Health science reports · 2025Article
- Search for common genetic variants to allow reliable Mendelian randomization investigations into ketone metabolism.European journal of epidemiology · 2025Article
- Genetic Risk Score Enables a Vaccine for Early Primary Prevention of CAD.Methodist DeBakey cardiovascular journal · 2025Review
- A translational framework of genoproteomic studies for cardiovascular drug discovery.NPJ cardiovascular health · 2024Article
- Unveiling promising drug targets for autism spectrum disorder: insights from genetics, transcriptomics, and proteomics.Briefings in bioinformatics · 2024Article
- Comment: Association Between Psoriasis and Non-Alcoholic Fatty Liver Disease: A Two-Sample Mendelian Randomization Study: Comment from Li et al [Letter].Clinical, cosmetic and investigational dermatology · 2024Article
- Causal associations of air pollution with rheumatoid arthritis: A transethnic Mendelian randomization study.PloS one · 2024Article
- Unraveling Potential Sex-Specific Effects of Cardiovascular Medications on Longevity Using Mendelian Randomization.Journal of the American Heart Association · 2023Article
- Evaluating a Causal Relationship between Complement Factor I Protein Level and Advanced Age-Related Macular Degeneration Using Mendelian Randomization.Ophthalmology science · 2022Article
- Genetic Risk Stratification: A Paradigm Shift in Prevention of Coronary Artery Disease.JACC. Basic to translational science · 2021Review
- Association Between Environmental Factors and Asthma Using Mendelian Randomization: Increased Effect of Body Mass Index on Adult-Onset Moderate-to-Severe Asthma Subtypes.Frontiers in genetics · 2021Article
- Genetic and phenotypic analysis of the causal relationship between aging and COVID-19.Communications medicine · 2021Article
- 15 years of genome-wide association studies and no signs of slowing down.Nature communications · 2020Article
- A Journey through Genetic Architecture and Predisposition of Coronary Artery Disease.Current genomics · 2020Review
- Genetically determined blood pressure, antihypertensive drug classes, and risk of stroke subtypes.Neurology · 2020Observational
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There has been a dearth of new drugs approved for cardiovascular disorders. The cost is prohibitive, averaging to $2.5 billion, and requiring 12.5 years. This is in large part due to the high failure rate, with only 5% approval by the Food and Drug Administration. Despite preclinical studies showing potential safety and efficacy, most fail when they go to clinical trials phase I to III. One cause for failure is the drug target, often discovered to be a biomarker rather than causative for the disease. Mendelian randomization (MR) studies would determine whether the drug target is causative and could save millions of dollars and time, and prevent unnecessary exposure to adverse drug effects. This was demonstrated in 3 clinical trials that were negative with 2 drugs, veraspladib and darapladib. MR studies during the trials showed the targets of secretory and lipoprotein-associated phospholipids A2 are not causative for coronary artery disease and predicted negative results. The requirement for MR studies is a genetic risk variant with altered function, randomized at conception that remains fixed throughout one's lifetime. It is not confounded by dietary, lifestyle, or socioeconomic factors. It is more sensitive than randomized controlled trials because exposure to the risk factor is fixed for a lifetime. MR studies showed plasma high-density lipoprotein cholesterol is not a causative target of coronary artery disease, and neither is uric acid, C-reactive protein, and others. MR studies are highly sensitive in determining whether drug targets are causative, and are relatively easy, inexpensive, and not time consuming. It is recommended that drug targets undergo MR studies before proceeding to randomized controlled trials.
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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.