ReviewNature reviews. Drug discovery2013
Validating therapeutic targets through human genetics.
Review in Nature reviews. Drug discovery, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 391 papers, 6 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.
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
391 citing papers in PubMed, 6 syntheses or guidelines pooled it.
- Improving reproducibility of differentially expressed genes in single-cell transcriptomic studies of neurodegenerative diseases through meta-analysis.Nature communications · 2025Pooled it
- Genetically proxied therapeutic inhibition of lipid-lowering drug targets and risk of rheumatoid arthritis disease: a Mendelian randomization study.Clinical rheumatology · 2024Pooled it
- Identification and single-base gene-editing functional validation of a cis-EPO variant as a genetic predictor for EPO-increasing therapies.American journal of human genetics · 2022Pooled it
- Charting the proteome landscape in major psychiatric disorders: From biomarkers to biological pathways towards drug discovery.European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2022Pooled it
- Pooled it
- Genetic Determinants for Bacterial Osteomyelitis: A Focused Systematic Review of Published Literature.Frontiers in genetics · 2021Pooled it
- The Genetic Architecture of Chronic Cough: From Sensory Hypersensitivity to Treatable Trait.Pulmonary therapy · 2026Review
- Deviations from genetic additivity driven by rare variants at biobank scale.Nature communications · 2026Article
- Multi-omics-driven precision medicine.iMeta · 2026Review
- Article
- A blended genome and exome sequencing method captures genetic variation in an unbiased and cost-effective manner.Nature genetics · 2026Article
- Buffering of gene dosage response curves for human complex traits.Cell genomics · 2026Article
- Exposome Versus Genome in HS: How Do We Currently Explain Where Disease Arises from?Journal of clinical medicine · 2026Review
- Gene dosage differences and non-linear impacts on complex traits.Cell genomics · 2026Article
- Target identification and assessment in the era of AI.Nature reviews. Drug discovery · 2026Review
- Genetically supported drug target prioritization for rare diseases.Genome medicine · 2026Article
- Deep mutational scanning reveals pharmacologically relevant insights into TYK2 signaling and disease.eLife · 2026Article
- A multi-ethnic reference map of T cell receptor germline diversity reveals evidence of natural selection on alpha chain genes.Nature communications · 2026Article
- Proxied therapeutic inhibition on sclerostin and atrial fibrillation risk.Communications medicine · 2026Article
- Comprehensive adjudication identifies 111 high-confidence loci for Alzheimer's disease and related dementias.medRxiv : the preprint server for health sciences · 2026Article
331 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
More than 90% of the compounds that enter clinical trials fail to demonstrate sufficient safety and efficacy to gain regulatory approval. Most of this failure is due to the limited predictive value of preclinical models of disease, and our continued ignorance regarding the consequences of perturbing specific targets over long periods of time in humans. 'Experiments of nature' - naturally occurring mutations in humans that affect the activity of a particular protein target or targets - can be used to estimate the probable efficacy and toxicity of a drug targeting such proteins, as well as to establish causal rather than reactive relationships between targets and outcomes. Here, we describe the concept of dose-response curves derived from experiments of nature, with an emphasis on human genetics as a valuable tool to prioritize molecular targets in drug development. We discuss empirical examples of drug-gene pairs that support the role of human genetics in testing therapeutic hypotheses at the stage of target validation, provide objective criteria to prioritize genetic findings for future drug discovery efforts and highlight the limitations of a target validation approach that is anchored in human genetics.
Indexed as
Identifiers
23868113What 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.