ArticleGenome medicine2022
Calculating variant penetrance from family history of disease and average family size in population-scale data.
Article in Genome medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- International policies guiding the selection, analysis, and clinical management of secondary findings from genomic sequencing: A systematic review.American journal of human genetics · 2024Pooled it
- Age-based risk estimates for C9orf72RE-related diseases: Theoretical developments and added value for genetic counseling.PLoS genetics · 2026Article
- High Prevalence of SOD1 Pathogenic Variants in the UK Biobank: Implications for Early Intervention in Amyotrophic Lateral Sclerosis.Annals of neurology · 2026Article
- Nerve Excitability in Asymptomatic Carriers and Amyotrophic Lateral Sclerosis Patients With C9orf72.Annals of clinical and translational neurology · 2025Article
- Design considerations for C9orf72 disease prevention trials.Brain : a journal of neurology · 2025Review
- Entering the era of precision medicine to treat amyotrophic lateral sclerosis.Molecular neurodegeneration · 2025Review
- Oligogenic structure of amyotrophic lateral sclerosis has genetic testing, counselling and therapeutic implications.Journal of neurology, neurosurgery, and psychiatry · 2025Article
- Machine learning-based penetrance of genetic variants.Science (New York, N.Y.) · 2025Article
- Modelling Population Genetic Screening in Rare Neurodegenerative Diseases.Biomedicines · 2025Article
- Clinical Outcome of Hypertrophic Cardiomyopathy in Probands with the Founder Variant c.913_914del in MYBPC3: A Slovenian Cohort Study.Journal of cardiovascular translational research · 2025Article
- Longitudinal Magnetic Resonance Imaging in Asymptomatic C9orf72 Mutation Carriers Distinguishes Phenoconverters to Amyotrophic Lateral Sclerosis or Amyotrophic Lateral Sclerosis With Frontotemporal Dementia.Annals of neurology · 2025Article
- Survey of service needs to embed genome sequencing for motor neuron disease in neurology in the English National Health Service.Journal of medical genetics · 2024Article
- Variability in SOD1-associated amyotrophic lateral sclerosis: geographic patterns, clinical heterogeneity, molecular alterations, and therapeutic implications.Translational neurodegeneration · 2024Review
- Traumatic injury causes selective degeneration and TDP-43 mislocalization in human iPSC-derivedbioRxiv : the preprint server for biology · 2024Article
- Personalised penetrance estimation for C9orf72-related amyotrophic lateral sclerosis and frontotemporal dementia.BMJ neurology open · 2024Article
- Calculating variant penetrance from family history of disease and average family size in population-scale data.Genome medicine · 2022Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundGenetic penetrance is the probability of a phenotype when harbouring a particular pathogenic variant. Accurate penetrance estimates are important across biomedical fields including genetic counselling, disease research, and gene therapy. However, existing approaches for penetrance estimation require, for instance, large family pedigrees or availability of large databases of people affected and not affected by a disease.
methodsWe present a method for penetrance estimation in autosomal dominant phenotypes. It examines the distribution of a variant among people affected (cases) and unaffected (controls) by a phenotype within population-scale data and can be operated using cases only by considering family disease history. It is validated through simulation studies and candidate variant-disease case studies.
resultsOur method yields penetrance estimates which align with those obtained via existing approaches in the Parkinson's disease LRRK2 gene and pulmonary arterial hypertension BMPR2 gene case studies. In the amyotrophic lateral sclerosis case studies, examining penetrance for variants in the SOD1 and C9orf72 genes, we make novel penetrance estimates which correspond closely to understanding of the disease.
conclusionsThe present approach broadens the spectrum of traits for which reliable penetrance estimates can be obtained. It has substantial utility for facilitating the characterisation of disease risks associated with rare variants with an autosomal dominant inheritance pattern. The yielded estimates avoid any kinship-specific effects and can circumvent ascertainment biases common when sampling rare variants among control populations.
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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.