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Dataset Details

Superfund Research Program

Title: DNA methylation distinguishes pathologically normal human tissues

Accession Number: GSE19434

Link to Dataset: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE19434

Repository: Gene Expression Omnibus (GEO)

Data Type(s): Gene Expression

Experiment Type(s): Methylation profiling by array

Organism(s): Homo sapiens

Summary: " Epigenetic control of gene transcription is critical for normal human development and cellular differentiation. While alterations of epigenetic marks such as DNA methylation have been linked to cancers and many other human diseases, interindividual epigenetic variation in normal tissues due to aging, environmental factors, or innate susceptibility are poorly characterized. The plasticity, tissue-specific nature, and variability of gene expression are related to epigenomic states that vary across individuals. Thus, population-based investigations are needed to further our understanding of the fundamental dynamics of normal individual epigenomes. We analyzed 217 non-pathologic human tissues from 10 anatomic sites at 1413 autosomal CpG loci associated with 773 genes to investigate tissue-specific differences in DNA methylation, and to discern how aging and exposures contribute to normal variation in methylation. Methylation profile classes derived from unsupervised modeling were significantly associated with age (P < 0.0001), and were significant predictors of tissue origin (P < 0.0001). In solid tissues (n=119) we found striking, highly significant CpG island dependent correlations between age and methylation; loci in CpG islands gained methylation with age, loci not in CpG islands lost methylation with age (P < 0.001), and this pattern was consistent across tissues and in an analysis of blood-derived DNA. Our data clearly demonstrate age and exposure related differences in tissue-specific methylation, and significant age associated methylation patterns which are CpG island context dependent. This work provides novel insight into the role of aging and the environment in susceptibility to diseases such as cancer, and critically informs the field of epigenomics by providing evidence of epigenetic dysregulation by age-related methylation alterations. Collectively we reveal key issues to consider both in the construction of reference."

Publication(s) associated with this dataset:
  • Christensen BC, Houseman EA, Marsit CJ, Zheng S, Wrensch MR, Wiemels JL, Nelson HH, Karagas MR, Padbury J, Bueno R, Sugarbaker DJ, Yeh R, Wiencke JK, Kelsey KT. 2009. Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet 5(8):e1000602. doi:10.1371/journal.pgen.1000602 PMID:19680444 PMCID:PMC2718614
Project(s) associated with this dataset:
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