ArticleScience (New York, N.Y.)2016
Health and population effects of rare gene knockouts in adult humans with related parents.
Article in Science (New York, N.Y.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 187 papers, 4 of them syntheses 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
187 citing papers in PubMed, 4 syntheses or guidelines pooled it, 310 citations in OpenAlex.
- Meta-analysis across six global biobanks identifies recessive coding associations with complex traits and diseases.American journal of human genetics · 2026Pooled it
- NAT2 global landscape: Genetic diversity and acetylation statuses from a systematic review.PloS one · 2023Pooled it
- Associations of autozygosity with a broad range of human phenotypes.Nature communications · 2019Pooled it
- A scientometric review of genome-wide association studies.Communications biology · 2019Pooled it
- PRDM9-mediated meiotic hotspot specification is constrained in humans despite extensive sequence diversity.bioRxiv : the preprint server for biology · 2026Article
- Article
- Article
- Systematic analysis of homozygous autosomal copy number losses in exomes improves diagnostic yield and uncovers ultra-rare recessive disorders.European journal of human genetics : EJHG · 2026Article
- On the origin of PRDM9-guided recombination hotspots.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Exome sequencing and analysis of 44,028 British South Asians enriched for high autozygosity.Nature genetics · 2026Article
- Proteome-Wide Analysis of Human Deletions.Proteins · 2026Article
- Transposable elements contribute substantially to naturally occurring genetic lethality in Drosophila melanogaster.PLoS biology · 2026Article
- The OurHealth Study: A digital genomic cohort for cardiometabolic risk mechanisms in US South Asians.NPJ digital medicine · 2026Review
- The biomedical landscape of genomic structural variation in the qatari population.Nature communications · 2026Article
- Heterozygous PRDM9 truncating variant in a patient with primary ovarian insufficiency.Journal of human genetics · 2025Article
- Insights from human NF-κB knockouts.EMBO reports · 2025Review
- Bi-allelic variants in BRF2 are associated with perinatal death and craniofacial anomalies.Genome medicine · 2025Article
- PON-P3: Accurate Prediction of Pathogenicity of Amino Acid Substitutions.International journal of molecular sciences · 2025Article
- Article
- There will always be variants of uncertain significance. Analysis of VUSs.NAR genomics and bioinformatics · 2024Article
127 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
36 authors at 12 institutions in 2 countries.
Funding
Abstract
Examining complete gene knockouts within a viable organism can inform on gene function. We sequenced the exomes of 3222 British adults of Pakistani heritage with high parental relatedness, discovering 1111 rare-variant homozygous genotypes with predicted loss of function (knockouts) in 781 genes. We observed 13.7% fewer homozygous knockout genotypes than we expected, implying an average load of 1.6 recessive-lethal-equivalent loss-of-function (LOF) variants per adult. When genetic data were linked to the individuals' lifelong health records, we observed no significant relationship between gene knockouts and clinical consultation or prescription rate. In this data set, we identified a healthy PRDM9-knockout mother and performed phased genome sequencing on her, her child, and control individuals. Our results show that meiotic recombination sites are localized away from PRDM9-dependent hotspots. Thus, natural LOF variants inform on essential genetic loci and demonstrate PRDM9 redundancy in humans.
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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.