ReviewNature2023
From target discovery to clinical drug development with human genetics.
Review in Nature, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers, 1 of them a synthesis 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
128 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Multi-ancestry whole genome sequencing analysis of lean body mass.Genome biology · 2025Pooled it
- Unveiling the impact of colonic pH and pH-sensing receptors in blood pressure regulation.Gut microbes · 2026Review
- Epigenetic silencingCancer biology & therapy · 2026Article
- Genome-scale perturbation signatures from primary human CD4bioRxiv : the preprint server for biology · 2026Article
- Proteome-wide Mendelian randomization identifies APOM and TNXB as actionable mediators of steroid-sensitive nephrotic syndrome.Pediatric nephrology (Berlin, Germany) · 2026Article
- The Case for Master Protocols for Rare Neurological Diseases.Annals of neurology · 2026Review
- Cell-type specific analyses in blood and gut identify cis-eQTL matching 140 IBD risk loci and entrectinib as repurposing candidate.Nature communications · 2026Article
- Partitioned blood pressure polygenic risk reveals differential genetic effects of tissue-specific enhancers and their interactions on cardiovascular disease.Research square · 2026Article
- Locus-specific stratification and prioritization unveil genetic risk mechanism underlying complex diseases.Nature communications · 2026Article
- Large-scale admixture mapping in the All of Us Research Program improves the characterization of cross-population phenotypic differences.Nature communications · 2026Article
- Article
- Post-Marketing Requirements for Anticancer Drugs Approved in Japan, 2001-2024: A Cross-Sectional Analysis.CPT: pharmacometrics & systems pharmacology · 2026Article
- Repurposing trazodone for Alzheimer's disease to modulate soluble ST2 levels and alleviate Alzheimer's pathology.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- Integrative multi-omics reveals MHC class II-mediated neuroinflammation and systemic metabolic dysregulation as transdiagnostic drivers in major brain disorders.Translational psychiatry · 2026Article
- Translating genome-wide association studies at multiple scales: Drug target prioritization, cellular architectures, and organ imaging.Cell genomics · 2026Review
- A comprehensive overview of the biological foundations of ADHD.Bioscience reports · 2026Review
- Long-term restoration of auditory function in a DFNA2 mouse model by adenine base editing.EMBO molecular medicine · 2026Article
- Germline mutations and somatic mosaicism in steatotic liver diseases and related liver carcinogenesis.Nature reviews. Gastroenterology & hepatology · 2026Review
- Proteome-wide genetic study identified therapeutic targets for early-onset and late-onset Alzheimer's disease.International journal of surgery (London, England) · 2026Article
68 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
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The substantial investments in human genetics and genomics made over the past three decades were anticipated to result in many innovative therapies. Here we investigate the extent to which these expectations have been met, excluding cancer treatments. In our search, we identified 40 germline genetic observations that led directly to new targets and subsequently to novel approved therapies for 36 rare and 4 common conditions. The median time between genetic target discovery and drug approval was 25 years. Most of the genetically driven therapies for rare diseases compensate for disease-causing loss-of-function mutations. The therapies approved for common conditions are all inhibitors designed to pharmacologically mimic the natural, disease-protective effects of rare loss-of-function variants. Large biobank-based genetic studies have the power to identify and validate a large number of new drug targets. Genetics can also assist in the clinical development phase of drugs-for example, by selecting individuals who are most likely to respond to investigational therapies. This approach to drug development requires investments into large, diverse cohorts of deeply phenotyped individuals with appropriate consent for genetically assisted trials. A robust framework that facilitates responsible, sustainable benefit sharing will be required to capture the full potential of human genetics and genomics and bring effective and safe innovative therapies to patients quickly.
Indexed as
Identifiers
37612393What 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.