ArticlePLoS genetics2014
Genetic analysis of the cardiac methylome at single nucleotide resolution in a model of human cardiovascular disease.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
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- Targeting TET3 suppresses group 3 medulloblastoma stemness and progression via impairing hypomethylation of Otx2 super-enhancer.Cell reports. Medicine · 2025Article
- DNA Methylation of Somatic Tissues in Oysters is Influenced by Sex and Heredity.Marine biotechnology (New York, N.Y.) · 2025Article
- Cap analysis of gene expression reveals alternative promoter usage in a rat model of hypertension.Life science alliance · 2022Article
- Genetic Complementation of ATP Synthase Deficiency Due to Dysfunction of TMEM70 Assembly Factor in Rat.Biomedicines · 2022Article
- Epigenetic inheritance of acquired traits through DNA methylation.Animal frontiers : the review magazine of animal agriculture · 2021Article
- Evolutionary epigenomic analyses in mammalian early embryos reveal species-specific innovations and conserved principles of imprinting.Science advances · 2021Article
- DNA methylation in mice is influenced by genetics as well as sex and life experience.Nature communications · 2019Article
- Systems Genetics Approaches in Rat Identify Novel Genes and Gene Networks Associated With Cardiac Conduction.Journal of the American Heart Association · 2018Article
- Genomic approaches for the elucidation of genes and gene networks underlying cardiovascular traits.Biophysical reviews · 2018Review
- Evolutionary expansion of DNA hypomethylation in the mammalian germline genome.Genome research · 2018Article
- Genome-wide discovery of long intergenic noncoding RNAs and their epigenetic signatures in the rat.Scientific reports · 2017Article
- Changes in the Coding and Non-coding Transcriptome and DNA Methylome that Define the Schwann Cell Repair Phenotype after Nerve Injury.Cell reports · 2017Article
- A Bayesian Approach for Analysis of Whole-Genome Bisulfite Sequencing Data Identifies Disease-Associated Changes in DNA Methylation.Genetics · 2017Article
- From integrative genomics to systems genetics in the rat to link genotypes to phenotypes.Disease models & mechanisms · 2016Review
- Single Base-Resolution Methylome of the Dizygotic Sheep.PloS one · 2015Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Epigenetic marks such as cytosine methylation are important determinants of cellular and whole-body phenotypes. However, the extent of, and reasons for inter-individual differences in cytosine methylation, and their association with phenotypic variation are poorly characterised. Here we present the first genome-wide study of cytosine methylation at single-nucleotide resolution in an animal model of human disease. We used whole-genome bisulfite sequencing in the spontaneously hypertensive rat (SHR), a model of cardiovascular disease, and the Brown Norway (BN) control strain, to define the genetic architecture of cytosine methylation in the mammalian heart and to test for association between methylation and pathophysiological phenotypes. Analysis of 10.6 million CpG dinucleotides identified 77,088 CpGs that were differentially methylated between the strains. In F1 hybrids we found 38,152 CpGs showing allele-specific methylation and 145 regions with parent-of-origin effects on methylation. Cis-linkage explained almost 60% of inter-strain variation in methylation at a subset of loci tested for linkage in a panel of recombinant inbred (RI) strains. Methylation analysis in isolated cardiomyocytes showed that in the majority of cases methylation differences in cardiomyocytes and non-cardiomyocytes were strain-dependent, confirming a strong genetic component for cytosine methylation. We observed preferential nucleotide usage associated with increased and decreased methylation that is remarkably conserved across species, suggesting a common mechanism for germline control of inter-individual variation in CpG methylation. In the RI strain panel, we found significant correlation of CpG methylation and levels of serum chromogranin B (CgB), a proposed biomarker of heart failure, which is evidence for a link between germline DNA sequence variation, CpG methylation differences and pathophysiological phenotypes in the SHR strain. Together, these results will stimulate further investigation of the molecular basis of locally regulated variation in CpG methylation and provide a starting point for understanding the relationship between the genetic control of CpG methylation and disease phenotypes.
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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.