ArticleScience (New York, N.Y.)2023
Rare penetrant mutations confer severe risk of common diseases.
Article in Science (New York, N.Y.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Development and validation of a multiancestry and multitrait polygenic risk score for lung cancer.Nature communications · 2026Pooled it
- A heritability-optimized method for functional prioritization of rare coding variants in complex traits.Nature genetics · 2026Article
- Post-genome-wide association study variant-to-function challenges in asthma research.The Journal of allergy and clinical immunology · 2026Review
- Rare variant effect estimation and polygenic risk prediction.Nature genetics · 2026Article
- Evolution of quantitative traits with background selection.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Non-Invasive Measures of DNA Methylation Capture Molecular Aging in Wild Capuchin Monkeys.Molecular ecology · 2026Article
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- Review
- Article
- Shared genetic architecture and pathways linking major depressive disorder and autoimmune thyroid disease: insights from common and rare variants.Translational psychiatry · 2026Article
- The Biobank Rare Variant consortium powers the discovery of rare genetic associations through global collaboration.medRxiv : the preprint server for health sciences · 2026Article
- Gene-gene interactions between a LMNA variant and common polymorphisms drive early-onset atrial fibrillation.Nature communications · 2026Article
- Integrating common and rare variants improves polygenic risk prediction across diverse populations.Nature communications · 2026Article
- Common and rare genetic variants show network convergence for a majority of human traits.EMBO reports · 2026Article
- Mapping epigenetic gene variant dynamics: comparative analysis of frequency, functional impact and trait associations in African and European populations.Scientific reports · 2026Article
- Leveraging protein language models to identify complex trait associations with previously inaccessible classes of functional rare variants.Cell genomics · 2026Article
- Fifty Shades of Risk: Population Studies and the Genetic Architecture of Kidney Diseases.Journal of the American Society of Nephrology : JASN · 2026Review
- The polygenic, omnigenic and stratagenic models of complex disease risk.Nature genetics · 2026Review
- Clinical implications of rare and common variation in preimplantation genetic testing for breast cancer.NPJ genomic medicine · 2026Article
- Article
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Authors and funding
21 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We examined 454,712 exomes for genes associated with a wide spectrum of complex traits and common diseases and observed that rare, penetrant mutations in genes implicated by genome-wide association studies confer ~10-fold larger effects than common variants in the same genes. Consequently, an individual at the phenotypic extreme and at the greatest risk for severe, early-onset disease is better identified by a few rare penetrant variants than by the collective action of many common variants with weak effects. By combining rare variants across phenotype-associated genes into a unified genetic risk model, we demonstrate superior portability across diverse global populations compared with common-variant polygenic risk scores, greatly improving the clinical utility of genetic-based risk prediction.
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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.