ArticleGenetics in medicine : official journal of the American College of Medical Genetics2016
The promise and peril of genomic screening in the general population.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
What it found
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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
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- A systematic review of the methodological quality of economic evaluations in genetic screening and testing for monogenic disorders.Genetics in medicine : official journal of the American College of Medical Genetics · 2022Pooled it
- Newborn Sequencing in Genomic Medicine and Public Health.Pediatrics · 2017Trial
- Deciding "what" to screen for and "when": The importance of natural history information.American journal of human genetics · 2026Review
- Three ethical approaches to expanding newborn screening through genomics: a critical comparative analysis.BMC medical ethics · 2025Article
- Clinical Strategies in Gene Screening Counseling for the Healthy General Population.Korean journal of family medicine · 2024Article
- Characterizing the pathogenicity of genetic variants: the consequences of context.NPJ genomic medicine · 2024Article
- Building a vertically integrated genomic learning health system: The biobank at the Colorado Center for Personalized Medicine.American journal of human genetics · 2024Article
- Combinatorial batching of DNA for ultralow-cost detection of pathogenic variants.Genome medicine · 2023Article
- The promise of public health ethics for precision medicine: the case of newborn preventive genomic sequencing.Human genetics · 2022Review
- Public Interest in Population Genetic Screening for Cancer Risk.Frontiers in genetics · 2022Article
- Physician-directed genetic screening to evaluate personal risk for medically actionable disorders: a large multi-center cohort study.BMC medicine · 2021Article
- DNA-based screening and personal health: a points to consider statement for individuals and health-care providers from the American College of Medical Genetics and Genomics (ACMG).Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
- Assessing the implications of positive genomic screening results.Personalized medicine · 2020Article
- An Age-Based Framework for Evaluating Genome-Scale Sequencing Results in Newborn Screening.The Journal of pediatrics · 2019Article
- Predispositional genome sequencing in healthy adults: design, participant characteristics, and early outcomes of the PeopleSeq Consortium.Genome medicine · 2019Article
- Reconciling Opportunistic and Population Screening in Clinical Genomics.Mayo Clinic proceedings · 2019Review
- High-frequency actionable pathogenic exome variants in an average-risk cohort.Cold Spring Harbor molecular case studies · 2018Article
- Age and perceived risks and benefits of preventive genomic screening.Genetics in medicine : official journal of the American College of Medical Genetics · 2018Article
- Genomic Screening: The Mutation and the Mustard Seed.The Journal of law, medicine & ethics : a journal of the American Society of Law, Medicine & Ethics · 2018Article
- Identification of Misclassified ClinVar Variants via Disease Population Prevalence.American journal of human genetics · 2018Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
purposeUtilization of sequencing to screen the general population for preventable monogenic conditions is receiving substantial attention because of its potential to decrease morbidity and mortality. However, the selection of which variants to return is a serious implementation challenge. Procedures must be investigated to ensure optimal test characteristics and avoidance of harm from false-positive test results.
methodsWe scanned exome sequences from 478 well-phenotyped individuals for potentially pathogenic variants in 17 genes representing 11 conditions that are among the most medically actionable Mendelian disorders in adults. We developed five variant selection algorithms with increasing sensitivity and measured their specificity in these 17 genes.
resultsVariant selection algorithms with increasing sensitivity exhibited decreased specificity, and performance was highly dependent on the genes analyzed. The most sensitive algorithm ranged from 88.8 to 99.6% specificity among the 17 genes.
conclusionFor conditions with very low prevalence, small reductions in specificity greatly increase false positives. This inescapable test characteristic governs the predictive value of genomic sequencing in the general population. To address this issue, test performance must be evaluated systematically for each condition so that the false negatives and false positives can be tailored for optimal outcomes, depending on the downstream clinical consequences.Genet Med 18 6, 593-599.
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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.