title: Concordant and discordant DNA methylation signatures of aging in human blood and brain.
abstract: 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.
authors.affiliation: Department of Physics, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6 Canada.
authors.forename: Pau
authors.initials: P
authors.lastname: Farré
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Child & Family Research Institute, 950 W 28th ave, Vancouver, BC V5Z4H4 Canada ; Department of Medical Genetics, University of British Columbia, 950 W 28th ave, Vancouver, BC V5Z4H4 Canada.
authors.forename: Meaghan J
authors.initials: MJ
authors.lastname: Jones
authors.affiliation: Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, 6875 Boulevard Lasalle, Verdun, QC H4H 1R3 Canada ; Singapore Institute for Clinical Sciences, 30 Medical Drive, Singapore, 117609 Singapore ; Canadian Institute for Advanced Research, Toronto, ON Canada.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Meaney
authors.affiliation: Department of Physics, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6 Canada.
authors.forename: Eldon
authors.initials: E
authors.lastname: Emberly
authors.affiliation: Department of Psychiatry, McGill University, 6875 Boulevard Lasalle, Verdun, QC H4H 1R3 Canada.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Turecki
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Child & Family Research Institute, 950 W 28th ave, Vancouver, BC V5Z4H4 Canada ; Department of Medical Genetics, University of British Columbia, 950 W 28th ave, Vancouver, BC V5Z4H4 Canada ; Canadian Institute for Advanced Research, Toronto, ON Canada.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kobor
keywords: Aging; Blood; Brain; DNA methylation; Epigenetics; Principal component analysis