ArticleAmerican journal of human genetics2014
Pathogenic variants for Mendelian and complex traits in exomes of 6,517 European and African Americans: implications for the return of incidental results.
Article in American journal of human genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed.
- Evaluation of reported pathogenic variants and their frequencies in a Japanese population based on a whole-genome reference panel of 2049 individuals.Journal of human genetics · 2018Trial
- Genomic landscape of drug binding and pharmacogenetic variation across diverse populations using SNPdrug3D.Nature communications · 2026Article
- Inherited burden for disease predisposition in diverse populations.NPJ genomic medicine · 2026Article
- Leveraging underrepresented population data improves interpretation of genetic variants associated with hearing loss.Scientific reports · 2025Article
- Case report: A case of holocarboxylase synthetase deficiency with respiratory tract as the initial symptom.Frontiers in genetics · 2024Article
- Ethical, legal, and social implications of genetic risk prediction for multifactorial disease: a narrative review identifying concerns about interpretation and use of polygenic scores.Journal of community genetics · 2023Article
- MMADHC premature termination codons in the pathogenesis of cobalamin D disorder: Potential of translational readthrough reconstitution.Molecular genetics and metabolism reports · 2021Article
- The Human Gene Mutation Database (HGMDHuman genetics · 2020Review
- The role of exome sequencing in newborn screening for inborn errors of metabolism.Nature medicine · 2020Article
- A novel Romani microdeletion variant in the promoter sequence ofMolecular genetics and metabolism reports · 2020Article
- Genetic tests by next-generation sequencing in children with developmental delay and/or intellectual disability.Clinical and experimental pediatrics · 2020Article
- Article
- Worldwide carrier frequency and genetic prevalence of autosomal recessive inherited retinal diseases.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Frequency of ClinVar Pathogenic Variants in Chronic Kidney Disease Patients Surveyed for Return of Research Results at a Cleveland Public Hospital.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2020Article
- Challenges and Considerations in Sequence Variant Interpretation for Mendelian Disorders.Annals of laboratory medicine · 2019Review
- Standardized Biogeographic Grouping System for Annotating Populations in Pharmacogenetic Research.Clinical pharmacology and therapeutics · 2019Article
- Co-Occurrence of Leber Congenital Amaurosis and Meckel Syndrome Type 1 in a Fetus: Is There a Lesson to Be Learned?Molecular syndromology · 2019Article
- Functional Characterization of Glucocorticoid Receptor Variants Is Required to Avoid Misinterpretation of NGS Data.Journal of the Endocrine Society · 2019Article
- Estimating carrier frequencies of newborn screening disorders using a whole-genome reference panel of 3552 Japanese individuals.Human genetics · 2019Article
- Genomic sequencing identifies secondary findings in a cohort of parent study participants.Genetics in medicine : official journal of the American College of Medical Genetics · 2018Article
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Authors and funding
12 authors.
Funding
Abstract
Exome sequencing (ES) is rapidly being deployed for use in clinical settings despite limited empirical data about the number and types of incidental results (with potential clinical utility) that could be offered for return to an individual. We analyzed deidentified ES data from 6,517 participants (2,204 African Americans and 4,313 European Americans) from the National Heart, Lung, and Blood Institute Exome Sequencing Project. We characterized the frequencies of pathogenic alleles in genes underlying Mendelian conditions commonly assessed by newborn-screening (NBS, n = 39) programs, genes associated with age-related macular degeneration (ARMD, n = 17), and genes known to influence drug response (PGx, n = 14). From these 70 genes, we identified 10,789 variants and curated them by manual review of OMIM, HGMD, locus-specific databases, or primary literature to a total of 399 validated pathogenic variants. The mean number of risk alleles per individual was 15.3. Every individual had at least five known PGx alleles, 99% of individuals had at least one ARMD risk allele, and 45% of individuals were carriers for at least one pathogenic NBS allele. The carrier burden for severe recessive childhood disorders was 0.57. Our results demonstrate that risk alleles of potential clinical utility for both Mendelian and complex traits are detectable in every individual. These findings highlight the necessity of developing guidelines and policies that consider the return of results to all individuals and underscore the need to develop innovative approaches and tools that enable individuals to exercise their choice about the return of incidental results.
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