ArticleAmerican journal of human genetics2015
Individualized iterative phenotyping for genome-wide analysis of loss-of-function mutations.
Article in American journal of human genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03276637 (The MilSeq Project), which is not on this map. Cited by 53 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.
The MilSeq Project: Enabling Personalized Medicine Through Exome Sequencing in the U.S. Air Force
Who cites it
53 citing papers in PubMed, 67 citations in OpenAlex.
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- Genetics and Traumatic Brain Injury: Findings from an Exome-Based Study of a 50-Patient Case Series.Current issues in molecular biology · 2024Article
- Derived myeloid lineage induced pluripotent stem as a platform to study human C-C chemokine receptor type 5Δ32 homozygotes.iScience · 2023Article
- Perspectives on the future of dysmorphology.American journal of medical genetics. Part A · 2023Article
- COVID-19 severity: does the genetic landscape of rare variants matter?Frontiers in genetics · 2023Article
- Noninvasive prenatal diagnosis targeting fetal nucleated red blood cells.Journal of nanobiotechnology · 2022Review
- The Pathological Mechanisms of Hearing Loss Caused byBiomedicines · 2022Review
- Prevalence and Phenotypic Effects of Copy Number Variants in Isolated Hypogonadotropic Hypogonadism.The Journal of clinical endocrinology and metabolism · 2022Article
- Incomplete Penetrance and Variable Expressivity: From Clinical Studies to Population Cohorts.Frontiers in genetics · 2022Review
- A study of elective genome sequencing and pharmacogenetic testing in an unselected population.Molecular genetics & genomic medicine · 2021Article
- A Case Series of FamilialGenes · 2021Article
- Penetrance and outcomes at 1-year following return of actionable variants identified by genome sequencing.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
- Engagement and return of results preferences among a primarily African American genomic sequencing research cohort.American journal of human genetics · 2021Article
- Increased Burden of Rare Sequence Variants in GnRH-Associated Genes in Women With Hypothalamic Amenorrhea.The Journal of clinical endocrinology and metabolism · 2021Article
- Clinical outcomes of a genomic screening program for actionable genetic conditions.Genetics in medicine : official journal of the American College of Medical Genetics · 2020Observational
- An assessment of the role of vinculin loss of function variants in inherited cardiomyopathy.Human mutation · 2020Article
- Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Clinical and Genomic Evaluation of 207 Genetic Myopathies in the Indian Subcontinent.Frontiers in neurology · 2020Article
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 2 countries.
Funding
Abstract
Next-generation sequencing provides the opportunity to practice predictive medicine based on identified variants. Putative loss-of-function (pLOF) variants are common in genomes and understanding their contribution to disease is critical for predictive medicine. To this end, we characterized the consequences of pLOF variants in an exome cohort by iterative phenotyping. Exome data were generated on 951 participants from the ClinSeq cohort and filtered for pLOF variants in genes likely to cause a phenotype in heterozygotes. 103 of 951 exomes had such a pLOF variant and 79 participants were evaluated. Of those 79, 34 had findings or family histories that could be attributed to the variant (28 variants in 18 genes), 2 had indeterminate findings (2 variants in 2 genes), and 43 had no findings or a negative family history for the trait (34 variants in 28 genes). The presence of a phenotype was correlated with two mutation attributes: prior report of pathogenicity for the variant (p = 0.0001) and prior report of other mutations in the same exon (p = 0.0001). We conclude that 1/30 unselected individuals harbor a pLOF mutation associated with a phenotype either in themselves or their family. This is more common than has been assumed and has implications for the setting of prior probabilities of affection status for predictive medicine.
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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.