Concordant and discordant DNA methylation signatures of aging in human blood and brain.

TitleConcordant and discordant DNA methylation signatures of aging in human blood and brain.
Publication TypeJournal Article
Year of Publication2015
AuthorsFarré P, Jones MJ, Meaney MJ, Emberly E, Turecki G, Kobor MS
JournalEpigenetics Chromatin
Date Published2015

BACKGROUND: DNA methylation is an epigenetic mark that balances plasticity with stability. While DNA methylation exhibits tissue specificity, it can also vary with age and potentially environmental exposures. In studies of DNA methylation, samples from specific tissues, especially brain, are frequently limited and so surrogate tissues are often used. As yet, we do not fully understand how DNA methylation profiles of these surrogate tissues relate to the profiles of the central tissue of interest.RESULTS: We have adapted principal component analysis to analyze data from the Illumina 450K Human Methylation array using a set of 17 individuals with 3 brain regions and whole blood. All of the top five principal components in our analysis were associated with a variable of interest: principal component 1 (PC1) differentiated brain from blood, PCs 2 and 3 were representative of tissue composition within brain and blood, respectively, and PCs 4 and 5 were associated with age of the individual (PC4 in brain and PC5 in both brain and blood). We validated our age-related PCs in four independent sample sets, including additional brain and blood samples and liver and buccal cells. Gene ontology analysis of all five PCs showed enrichment for processes that inform on the functions of each PC.CONCLUSIONS: Principal component analysis (PCA) allows simultaneous and independent analysis of tissue composition and other phenotypes of interest. We discovered an epigenetic signature of age that is not associated with cell type composition and required no correction for cellular heterogeneity.

Alternate JournalEpigenetics Chromatin
PubMed ID25977707
PubMed Central IDPMC4430927