ArticleAmerican journal of human genetics2018
Profiling and Leveraging Relatedness in a Precision Medicine Cohort of 92,455 Exomes.
Article in American journal of human genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
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- Genotype-first approach reveals monogenic lipodystrophy is underdiagnosed, with health and mortality risks.EBioMedicine · 2026Observational
- Widespread distribution of Alu/Alu-mediated genomic rearrangement predisposing to a broad range of Mendelian disease and cancer in human populations.Genome medicine · 2026Article
- APOE ε4 and Accelerated Cognitive Decline Among Cognitively Healthy Middle-Aged and Older Adults.JAMA network open · 2026Article
- Evidence of variations in genetic prevalence for loss-of-functionGenetics in medicine open · 2026Article
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- Genetic variants predisposing to an increased risk of kidney stone disease.The Journal of clinical investigation · 2025Article
- Rare missense variants inJournal of medical genetics · 2025Article
- TERT c.3150 G > C (p.K1050N): a founder Ashkenazi Jewish variant associated with telomere biology disorders.NPJ genomic medicine · 2025Article
- Genome-First Approach to Rare and Common Variant Risk of Thoracic Aortic Aneurysm and Dissection.medRxiv : the preprint server for health sciences · 2025Article
- A rare variant inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- A comparison of genome-wide association analyses of persistent symptoms after Lyme disease, fibromyalgia, and myalgic encephalomyelitis - chronic fatigue syndrome.BMC infectious diseases · 2025Article
- Phenotypic findings associated with variation in elastin.HGG advances · 2025Article
- CORRECTING MODEL MISSPECIFICATION IN RELATIONSHIP ESTIMATES.bioRxiv : the preprint server for biology · 2024Article
- Building a vertically integrated genomic learning health system: The biobank at the Colorado Center for Personalized Medicine.American journal of human genetics · 2024Article
- A genome-first approach to characterize DICER1 pathogenic variant prevalence, penetrance and cancer, thyroid, and other phenotypes in 2 population-scale cohorts.Genetics in medicine open · 2024Article
- Article
Corrections and comments
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Authors and funding
27 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Large-scale human genetics studies are ascertaining increasing proportions of populations as they continue growing in both number and scale. As a result, the amount of cryptic relatedness within these study cohorts is growing rapidly and has significant implications on downstream analyses. We demonstrate this growth empirically among the first 92,455 exomes from the DiscovEHR cohort and, via a custom simulation framework we developed called SimProgeny, show that these measures are in line with expectations given the underlying population and ascertainment approach. For example, within DiscovEHR we identified ∼66,000 close (first- and second-degree) relationships, involving 55.6% of study participants. Our simulation results project that >70% of the cohort will be involved in these close relationships, given that DiscovEHR scales to 250,000 recruited individuals. We reconstructed 12,574 pedigrees by using these relationships (including 2,192 nuclear families) and leveraged them for multiple applications. The pedigrees substantially improved the phasing accuracy of 20,947 rare, deleterious compound heterozygous mutations. Reconstructed nuclear families were critical for identifying 3,415 de novo mutations in ∼1,783 genes. Finally, we demonstrate the segregation of known and suspected disease-causing mutations, including a tandem duplication that occurs in LDLR and causes familial hypercholesterolemia, through reconstructed pedigrees. In summary, this work highlights the prevalence of cryptic relatedness expected among large healthcare population-genomic studies and demonstrates several analyses that are uniquely enabled by large amounts of cryptic relatedness.
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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.