ArticleNature genetics2016
Genome-wide significance testing of variation from single case exomes.
Article in Nature genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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.
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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
28 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A systematic review of the validated monogenic causes of human male infertility: 2020 update and a discussion of emerging gene-disease relationships.Human reproduction update · 2021Pooled it
- Benchmark of computational methods to detect digenism in sequencing data.European journal of human genetics : EJHG · 2025Review
- Diminished DNA binding affinity of DMRT1 caused by heterozygous DM domain mutations is a cause of male infertility.Human molecular genetics · 2025Article
- Easy-PSAP: An Integrated Workflow to Prioritize Pathogenic Variants in Sequence Data from a Single Individual.Human heredity · 2025Article
- PSAP-Genomic-Regions: A Method Leveraging Population Data to Prioritize Coding and Non-Coding Variants in Whole Genome Sequencing for Rare Disease Diagnosis.Genetic epidemiology · 2025Article
- C19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germ line.Molecular cell · 2024Article
- Deleterious genetic changes in AGTPBP1 result in teratozoospermia with sperm head and flagella defects.Journal of cellular and molecular medicine · 2024Article
- DDX3Y is likely the key spermatogenic factor in the AZFa region that contributes to human non-obstructive azoospermia.Communications biology · 2023Article
- Diverse monogenic subforms of human spermatogenic failure.Nature communications · 2022Article
- Rare variants and HLA haplotypes associated in patients with neuromyelitis optica spectrum disorders.Frontiers in immunology · 2022Article
- Calibrated rare variant genetic risk scores for complex disease prediction using large exome sequence repositories.Nature communications · 2021Article
- Recurrent Pregnancy Loss and Concealed Long-QT Syndrome.Journal of the American Heart Association · 2021Article
- VariantThe New England journal of medicine · 2021Article
- Strategies to Identify Genetic Variants Causing Infertility.Trends in molecular medicine · 2021Review
- Article
- Disease gene discovery in male infertility: past, present and future.Human genetics · 2021Review
- Disruption of human meiotic telomere complex genes TERB1, TERB2 and MAJIN in men with non-obstructive azoospermia.Human genetics · 2021Article
- A framework for high-resolution phenotyping of candidate male infertility mutants: from human to mouse.Human genetics · 2021Review
- Bi-allelic Mutations in M1AP Are a Frequent Cause of Meiotic Arrest and Severely Impaired Spermatogenesis Leading to Male Infertility.American journal of human genetics · 2020Article
- Mutation of CFAP57, a protein required for the asymmetric targeting of a subset of inner dynein arms in Chlamydomonas, causes primary ciliary dyskinesia.PLoS genetics · 2020Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Standard techniques from genetic epidemiology are ill-suited to formally assess the significance of variants identified from a single case. We developed a statistical inference framework for identifying unusual functional variation from a single exome or genome, what we refer to as the 'n-of-one' problem. Using this approach we assessed our ability to identify the causal genotypes in over 5 million simulated cases of Mendelian disease, identifying 39% of disease genotypes as the most damaging unit in a typical exome background. We applied our approach to 129 n-of-one families from the Undiagnosed Diseases Program, nominating 60% of 30 disease genes determined to be diagnostic by a standard clinical workup. Our method can currently produce well-calibrated P values when applied to single genomes, can facilitate integration of multiple data types for n-of-one analyses, and, with further work, could become a widely used epidemiological method like linkage analysis or genome-wide association analysis.
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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.