ArticlePLoS genetics2025
Human genetic evidence enriched for side effects of approved drugs.
Article in PLoS genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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.
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Who cites it
6 citing papers in PubMed.
- Single-cell multi-omic integration analysis prioritizes druggable genes and reveals cell-type-specific causal effects in glioblastomagenesis.Journal of translational medicine · 2026Article
- The Human Pleiotropic Map of GWAS Associations and Therapeutic Implications.bioRxiv : the preprint server for biology · 2026Article
- Genomics of drug target prioritization for complex diseases.Nature reviews. Genetics · 2026Review
- Gene Editing of Pluripotent Stem Cell-Derived Hepatic Cells for Liver Disease Modeling and Therapeutic Development.Biomolecules & therapeutics · 2026Review
- Development of a genetic priority score to predict drug side effects using human genetic evidence.Nature communications · 2025Article
- The Global Neurodegeneration Proteomics Consortium: biomarker and drug target discovery for common neurodegenerative diseases and aging.Nature medicine · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Safety failures are an important factor in low drug development success rates. Human genetic evidence can select drug targets causal in disease and enrich for successful programs. Here, we sought to determine whether human genetic evidence can also enrich for labeled side effects (SEs) of approved drugs. We combined the SIDER database of SEs with human genetic evidence from genome-wide association studies, Mendelian disease, and somatic mutations. SEs were 2.0 times more likely to occur for drugs whose target possessed human genetic evidence for a trait similar to the SE. Enrichment was highest when the trait and SE were most similar to each other, and was robust to removing drugs where the approved indication was also similar to the SE. The enrichment of genetic evidence was greatest for SEs that were more drug specific, affected more people, and were more severe. There was significant heterogeneity among disease areas the SEs mapped to, with the highest positive predictive value for cardiovascular SEs. This supports the integration of human genetic evidence early in the drug discovery process to identify potential SE risks to be monitored or mitigated in the course of drug development.
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What Socratic 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 Socratic graph.