ArticleAmerican journal of human genetics2020
A Survey of Rare Epigenetic Variation in 23,116 Human Genomes Identifies Disease-Relevant Epivariations and CGG Expansions.
Article in American journal of human genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 65 citations in OpenAlex.
- Multiomic approaches identify a rare CCG repeat expansion in BCLAF3 in neurodevelopmental disorders.Genome medicine · 2026Article
- Population epigenetics: deciphering DNA methylation diversity and its implications for health, disease, and evolution.Molecular biology and evolution · 2026Review
- Analysis Methods for Diagnosing Rare Neurodevelopmental Diseases with Episignatures: A Systematic Review of the Literature.Biomedicines · 2025Review
- Diagnosis of Angelman Syndrome, With 66 Years of Delay, Using Hypothesis-Free DNA Methylation Profiling.Clinical genetics · 2025Article
- Allelic expression patterns of imprinted and non-imprinted genes in cancer cell lines from multiple histologies.Clinical epigenetics · 2025Article
- Clinical evaluation of long-read sequencing-based episignature detection in developmental disorders.Genome medicine · 2025Article
- Expanding Upon Genomics in Rare Diseases: Epigenomic Insights.International journal of molecular sciences · 2024Review
- A phenome-wide association study of methylated GC-rich repeats identifies a GCC repeat expansion in AFF3 associated with intellectual disability.Nature genetics · 2024Article
- Methylated GCC repeat expansion in AFF3 associates with intellectual disability.Nature genetics · 2024Article
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- Pathogenic variants in KMT2C result in a neurodevelopmental disorder distinct from Kleefstra and Kabuki syndromes.American journal of human genetics · 2024Article
- Diagnostic utility of DNA methylation analysis in genetically unsolved pediatric epilepsies and CHD2 episignature refinement.Nature communications · 2024Article
- Unravelling the link between neurodevelopmental disorders and short tandem CGG-repeat expansions.Emerging topics in life sciences · 2023Review
- Polymorphic short tandem repeats make widespread contributions to blood and serum traits.Cell genomics · 2023Article
- Epimutation detection in the clinical context: guidelines and a use case from a new Bioconductor package.Epigenetics · 2023Article
- Redefining cerebral palsies as a diverse group of neurodevelopmental disorders with genetic aetiology.Nature reviews. Neurology · 2023Review
- Harnessing male germline epigenomics for the genetic improvement in cattle.Journal of animal science and biotechnology · 2023Review
- Stochastic epigenetic mutations as possible explanation for phenotypical discordance among twins with congenital hypothyroidism.Journal of endocrinological investigation · 2023Article
- Genome-wide evaluation of the effect of short tandem repeat variation on local DNA methylation.Genome research · 2023Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
Abstract
There is growing recognition that epivariations, most often recognized as promoter hypermethylation events that lead to gene silencing, are associated with a number of human diseases. However, little information exists on the prevalence and distribution of rare epigenetic variation in the human population. In order to address this, we performed a survey of methylation profiles from 23,116 individuals using the Illumina 450k array. Using a robust outlier approach, we identified 4,452 unique autosomal epivariations, including potentially inactivating promoter methylation events at 384 genes linked to human disease. For example, we observed promoter hypermethylation of BRCA1 and LDLR at population frequencies of ∼1 in 3,000 and ∼1 in 6,000, respectively, suggesting that epivariations may underlie a fraction of human disease which would be missed by purely sequence-based approaches. Using expression data, we confirmed that many epivariations are associated with outlier gene expression. Analysis of variation data and monozygous twin pairs suggests that approximately two-thirds of epivariations segregate in the population secondary to underlying sequence mutations, while one-third are likely sporadic events that occur post-zygotically. We identified 25 loci where rare hypermethylation coincided with the presence of an unstable CGG tandem repeat, validated the presence of CGG expansions at several loci, and identified the putative molecular defect underlying most of the known folate-sensitive fragile sites in the genome. Our study provides a catalog of rare epigenetic changes in the human genome, gives insight into the underlying origins and consequences of epivariations, and identifies many hypermethylated CGG repeat expansions.
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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.