ArticleNature communications2021
Contextualizing genetic risk score for disease screening and rare variant discovery.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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
18 citing papers in PubMed.
- Polygenic risk scores in human genetics for study design discovery and translation.Human genetics · 2026Review
- Genetic influences on haematopoiesis.Nature reviews. Genetics · 2026Review
- Clinical implications of rare and common variation in preimplantation genetic testing for breast cancer.NPJ genomic medicine · 2026Article
- Clinical implications of rare and common variation in preimplantation genetic testing for breast cancer.medRxiv : the preprint server for health sciences · 2025Article
- The Causal Pivot: A structural approach to genetic heterogeneity and variant discovery in complex diseases.American journal of human genetics · 2025Article
- Improving polygenic prediction from whole-genome sequencing data by leveraging predicted epigenomic features.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Scrutinizing neurodegenerative diseases: decoding the complex genetic architectures through a multi-omics lens.Human genomics · 2024Review
- Systematic assessment of COVID-19 host genetics using whole genome sequencing data.PLoS pathogens · 2024Article
- Genetic modifiers of rare variants in monogenic developmental disorder loci.Nature genetics · 2024Article
- Transcriptome-Wide Association Studies (TWAS): Methodologies, Applications, and Challenges.Current protocols · 2024Article
- Interrelationships Between Inflammatory Score, Delayed Cerebral Ischemia and Unfavorable Outcome in Patients with aSAH: A Four-Way Decomposition.Journal of inflammation research · 2024Article
- Identification of Rare Variants Involved in High Myopia Unraveled by Whole Genome Sequencing.Ophthalmology science · 2023Article
- A phenome-wide scan reveals convergence of common and rare variant associations.Genome medicine · 2023Article
- A Machine Learning Model to Aid Detection of Familial Hypercholesterolemia.JACC. Advances · 2023Article
- Exome-wide screening identifies novel rare risk variants for bone mineral density.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2023Article
- Exome-wide screening identifies novel rare risk variants for major depression disorder.Molecular psychiatry · 2022Article
- How Variation in Risk Allele Output and Gene Interactions Shape the Genetic Architecture of Schizophrenia.Genes · 2022Article
- Bench Research Informed by GWAS Results.Cells · 2021Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Studies of the genetic basis of complex traits have demonstrated a substantial role for common, small-effect variant polygenic burden (PB) as well as large-effect variants (LEV, primarily rare). We identify sufficient conditions in which GWAS-derived PB may be used for well-powered rare pathogenic variant discovery or as a sample prioritization tool for whole-genome or exome sequencing. Through extensive simulations of genetic architectures and generative models of disease liability with parameters informed by empirical data, we quantify the power to detect, among cases, a lower PB in LEV carriers than in non-carriers. Furthermore, we uncover clinically useful conditions wherein the risk derived from the PB is comparable to the LEV-derived risk. The resulting summary-statistics-based methodology (with publicly available software, PB-LEV-SCAN) makes predictions on PB-based LEV screening for 36 complex traits, which we confirm in several disease datasets with available LEV information in the UK Biobank, with important implications on clinical decision-making.
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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.