ArticleGenome biology2015
Population whole-genome bisulfite sequencing across two tissues highlights the environment as the principal source of human methylome variation.
Article in Genome biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Epigenome-wide meta-analysis of prenatal vitamin D insufficiency and cord blood DNA methylation.Epigenetics · 2024Pooled it
- Retroelement Hypomethylation Links Hypoxia Signaling, Immune Phenotypes, and Survival in Clear Cell Renal Cell Carcinoma.bioRxiv : the preprint server for biology · 2026Article
- Methylation patterns of the nasal epigenome of hospitalized SARS-CoV-2 positive patients reveal insights into molecular mechanisms of COVID-19.BMC medical genomics · 2025Article
- Genome-wide DNA methylation landscape of four Chinese populations and epigenetic variation linked to Tibetan high-altitude adaptation.Science China. Life sciences · 2023Article
- A functional genomics pipeline to identify high-value asthma and allergy CpGs in the human methylome.The Journal of allergy and clinical immunology · 2023Article
- Direct haplotype-resolved 5-base HiFi sequencing for genome-wide profiling of hypermethylation outliers in a rare disease cohort.Nature communications · 2023Article
- Systemic interindividual epigenetic variation in humans is associated with transposable elements and under strong genetic control.Genome biology · 2023Article
- Independent phenotypic plasticity axes define distinct obesity sub-types.Nature metabolism · 2022Article
- Tissue- and ethnicity-independent hypervariable DNA methylation states show evidence of establishment in the early human embryo.Nucleic acids research · 2022Article
- Differentially methylated CpGs in response to growth hormone administration in children with idiopathic short stature.Clinical epigenetics · 2022Article
- Overweight and obesity in pregnancy: their impact on epigenetics.European journal of clinical nutrition · 2021Review
- Revisiting genetic artifacts on DNA methylation microarrays exposes novel biological implications.Genome biology · 2021Article
- Immune cell residency in the nasal mucosa may partially explain respiratory disease severity across the age range.Scientific reports · 2021Article
- Atypical DNA methylation, sRNA-size distribution, and female gametogenesis in Utricularia gibba.Scientific reports · 2021Article
- Cognitive Impairment and Dementia After Stroke: Design and Rationale for the DISCOVERY Study.Stroke · 2021Review
- Exploring the evidence for epigenetic regulation of environmental influences on child health across generations.Communications biology · 2021Review
- DNA methylation profiles unique to Kalahari KhoeSan individuals.Epigenetics · 2021Article
- High-resolution epigenome analysis in nasal samples derived from children with respiratory viral infections reveals striking changes upon SARS-CoV-2 infection.medRxiv : the preprint server for health sciences · 2021Article
- Equivalent DNA methylation variation between monozygotic co-twins and unrelated individuals reveals universal epigenetic inter-individual dissimilarity.Genome biology · 2021Article
- Gut Microbiome: A Potential Indicator for Differential Diagnosis of Major Depressive Disorder and General Anxiety Disorder.Frontiers in psychiatry · 2021Article
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Authors and funding
20 authors.
Funding
Abstract
backgroundCpG methylation variation is involved in human trait formation and disease susceptibility. Analyses within populations have been biased towards CpG-dense regions through the application of targeted arrays. We generate whole-genome bisulfite sequencing data for approximately 30 adipose and blood samples from monozygotic and dizygotic twins for the characterization of non-genetic and genetic effects at single-site resolution.
resultsPurely invariable CpGs display a bimodal distribution with enrichment of unmethylated CpGs and depletion of fully methylated CpGs in promoter and enhancer regions. Population-variable CpGs account for approximately 15-20 % of total CpGs per tissue, are enriched in enhancer-associated regions and depleted in promoters, and single nucleotide polymorphisms at CpGs are a frequent confounder of extreme methylation variation. Differential methylation is primarily non-genetic in origin, with non-shared environment accounting for most of the variance. These non-genetic effects are mainly tissue-specific. Tobacco smoking is associated with differential methylation in blood with no evidence of this exposure impacting cell counts. Opposite to non-genetic effects, genetic effects of CpG methylation are shared across tissues and thus limit inter-tissue epigenetic drift. CpH methylation is rare, and shows similar characteristics of variation patterns as CpGs.
conclusionsOur study highlights the utility of low pass whole-genome bisulfite sequencing in identifying methylome variation beyond promoter regions, and suggests that targeting the population dynamic methylome of tissues requires assessment of understudied intergenic CpGs distal to gene promoters to reveal the full extent of inter-individual variation.
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