ArticleScience (New York, N.Y.)2012
An abundance of rare functional variants in 202 drug target genes sequenced in 14,002 people.
Article in Science (New York, N.Y.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 390 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
390 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Targeted Sequencing and Meta-Analysis of Preterm Birth.PloS one · 2016Pooled it
- Rare Functional Variants Associated with Antidepressant Remission in Mexican-Americans: Short title: Antidepressant remission and pharmacogenetics in Mexican-Americans.Journal of affective disorders · 2021Trial
- Charcot-Marie-Tooth gene, SBF2, associated with taxane-induced peripheral neuropathy in African Americans.Oncotarget · 2016Trial
- Revisiting retinal and macular degeneration in the genomics era.Nature reviews. Genetics · 2026Review
- Alternative tandem transcription initiation links noncoding variants to human disease through translational control.Nature communications · 2026Article
- Local ancestry-informed rare variant burden testing improves gene discovery in admixed populations.medRxiv : the preprint server for health sciences · 2026Article
- Hi-C informed kernel association test for integrating 3D genome structure into variant-set analysis.Briefings in bioinformatics · 2026Article
- Analysis of whole genome sequencing and plasma metabolomics unveil genetic determinants and clinical implications for human health.Nature communications · 2026Article
- Computing coalescence rates for complex demographies and sampling configurations.bioRxiv : the preprint server for biology · 2026Article
- The evolving landscape of pharmacogenomics: Current achievements and future directions.Pharmacological reviews · 2026Review
- The aspiration of precision glucocorticoid pharmacotherapy in immune-mediated diseases: where do we stand in integrating pharmacogenomics and biomarkers for individualized treatment?Frontiers in immunology · 2026Review
- Severity of effect considerations regarding the use of mutation as a toxicological endpoint for risk assessment: A report from the 8th International Workshop on Genotoxicity Testing (IWGT).Environmental and molecular mutagenesis · 2025Review
- Hi-C informed kernel association test: integrating 3-dimensional genome structure into variant-set association for whole-genome sequencing data.bioRxiv : the preprint server for biology · 2025Article
- Large-scale experimental assessment of variant effects on the structure and function of the citrate transporter SLC13A5.Science advances · 2025Article
- Study design and the sampling of deleterious rare variants in biobank-scale datasets.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Can AI reveal the next generation of high-impact bone genomics targets?Bone reports · 2025Review
- Pharmacogenetic Profiling of Genes Associated with Outcomes of Chemotherapy in Omani Healthy Controls.Genes · 2025Article
- Genetic Variation in Drug Targets: Are We Ready for the Era of Precision Medicinal Chemistry?ACS medicinal chemistry letters · 2025Article
- PathVar: A Customisable NGS Variant Calling Algorithm Implicates Novel Candidate Genes and Pathways in Hemiplegic Migraine.Clinical genetics · 2025Article
- Germline predisposition in multiple myeloma.iScience · 2025Article
330 more citing papers are in PubMed but not listed here.
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Authors and funding
31 authors.
Funding
Abstract
Rare genetic variants contribute to complex disease risk; however, the abundance of rare variants in human populations remains unknown. We explored this spectrum of variation by sequencing 202 genes encoding drug targets in 14,002 individuals. We find rare variants are abundant (1 every 17 bases) and geographically localized, so that even with large sample sizes, rare variant catalogs will be largely incomplete. We used the observed patterns of variation to estimate population growth parameters, the proportion of variants in a given frequency class that are putatively deleterious, and mutation rates for each gene. We conclude that because of rapid population growth and weak purifying selection, human populations harbor an abundance of rare variants, many of which are deleterious and have relevance to understanding disease risk.
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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.