ArticleNature medicine2023
Genetic association analysis of 77,539 genomes reveals rare disease etiologies.
Article in Nature medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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
59 citing papers in PubMed, 74 citations in OpenAlex.
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- From Spine to Syndrome: Incidental Spine MRI Red Flags Leading to PMEPA1-related Loeys-Dietz Syndrome.Internal medicine (Tokyo, Japan) · 2026Article
- Advancing risk gene discovery across the allele frequency spectrum.HGG advances · 2026Review
- Genetically supported drug target prioritization for rare diseases.Genome medicine · 2026Article
- Structural and Signaling Mechanisms of Aortic Wall Failure in Heritable Thoracic Aortic Disease.Cells · 2026Review
- Biallelic variants in RNU2-2 cause the most prevalent known recessive neurodevelopmental disorder.Nature genetics · 2026Article
- Could the Phenotypic Outcomes of Genetic Variability in Cells Operating in Mechanically Dynamic Environments be Influenced by a Disrupted "Cell-ECM" Relationship? Using Cystic Fibrosis and Marfan Syndrome as an Example.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Safeguarding lymphatic identity: cooperative Erg and Fli1 activity in lymphatic vascular homeostasis.The Journal of clinical investigation · 2026Article
- Cooperative ETS transcription factors are required for lymphatic endothelial cell integrity and resilience.The Journal of clinical investigation · 2026Article
- Genomics of drug target prioritization for complex diseases.Nature reviews. Genetics · 2026Review
- Loss-of-function variants in the CAPN1 activator CD99L2 cause X-linked spastic ataxia.Nature communications · 2026Article
- A Novel Homozygous Loss-of-Function Variant in GPR156 Delineates Non-syndromic Hearing Loss.Biochemical genetics · 2026Article
- GPR156 is required in sensory hair cells for proper auditory and vestibular function.Scientific reports · 2026Article
- Novel GJC2 and OBSCN variants co-segregating in a Chinese primary lymphedema pedigree.Orphanet journal of rare diseases · 2026Article
- Histone acetylation and methylation in rare diseases: from molecular mechanisms to clinical presentations.Frontiers in cell and developmental biology · 2026Review
- Further characterisation of immortalised human lymphatic endothelial cells to explore their transcriptomic profile and VEGFC response.Scientific reports · 2025Article
- Review
- Boosting the Power of Rare Variant Association Studies by Imputation Using Large-scale Sequencing Population.Genomics, proteomics & bioinformatics · 2025Article
- Zebrafish in neurodevelopmental disorders studies: Genetic models and pathological involvement of microglia.Developmental medicine and child neurology · 2025Review
Corrections and comments
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Authors and funding
34 authors at 17 institutions in 6 countries.
Funding
Abstract
The genetic etiologies of more than half of rare diseases remain unknown. Standardized genome sequencing and phenotyping of large patient cohorts provide an opportunity for discovering the unknown etiologies, but this depends on efficient and powerful analytical methods. We built a compact database, the 'Rareservoir', containing the rare variant genotypes and phenotypes of 77,539 participants sequenced by the 100,000 Genomes Project. We then used the Bayesian genetic association method BeviMed to infer associations between genes and each of 269 rare disease classes assigned by clinicians to the participants. We identified 241 known and 19 previously unidentified associations. We validated associations with ERG, PMEPA1 and GPR156 by searching for pedigrees in other cohorts and using bioinformatic and experimental approaches. We provide evidence that (1) loss-of-function variants in the Erythroblast Transformation Specific (ETS)-family transcription factor encoding gene ERG lead to primary lymphoedema, (2) truncating variants in the last exon of transforming growth factor-β regulator PMEPA1 result in Loeys-Dietz syndrome and (3) loss-of-function variants in GPR156 give rise to recessive congenital hearing impairment. The Rareservoir provides a lightweight, flexible and portable system for synthesizing the genetic and phenotypic data required to study rare disease cohorts with tens of thousands of participants.
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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 Socratic graph.