Factors underlying variable DNA methylation in a human community cohort

Lucia L. Lam, Eldon Emberly, Hunter B. Fraser, Sarah M. Neumann, Edith Chen, Gregory E. Miller*, Michael S. Kobor

*Corresponding author for this work

Research output: Contribution to journalArticle

266 Scopus citations

Abstract

Epigenetics is emerging as an attractive mechanism to explain the persistent genomic embedding of early-life experiences. Tightly linked to chromatin, which packages DNA into chromosomes, epigenetic marks primarily serve to regulate the activity of genes. DNA methylation is the most accessible and characterized component of the many chromatin marks that constitute the epigenome, making it an ideal target for epigenetic studies in human populations. Here, using peripheral blood mononuclear cells collected from a community-based cohort stratified for early-life socioeconomic status, we measured DNA methylation in the promoter regions of more than 14,000 human genes. Using this approach, we broadly assessed and characterized epigenetic variation, identified some of the factors that sculpt the epigenome, and determined its functional relation to gene expression.We found that the leukocyte composition of peripheral blood covaried with patterns of DNA methylation at many sites, as did demographic factors, such as sex, age, and ethnicity. Furthermore, psychosocial factors, such as perceived stress, and cortisol output were associated with DNA methylation, as was early-life socioeconomic status. Interestingly, we determined that DNA methylation was strongly correlated to the ex vivo inflammatory response of peripheral blood mononuclear cells to stimulation with microbial products that engage Toll-like receptors. In contrast, our work found limited effects of DNA methylation marks on the expression of associated genes across individuals, suggesting a more complex relationship than anticipated.

Original languageEnglish (US)
Pages (from-to)17253-17260
Number of pages8
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue numberSUPPL.2
DOIs
StatePublished - Oct 16 2012

Keywords

  • Early-life environment
  • Immune response
  • Population cohort

ASJC Scopus subject areas

  • General

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