Social and physical environments early in development predict DNA methylation of inflammatory genes in young adulthood

Thomas W. McDade*, Calen Ryan, Meaghan J. Jones, Julia L. MacIsaac, Alexander M. Morin, Jess M. Meyer, Judith B. Borja, Gregory E. Miller, Michael S. Kobor, Christopher W. Kuzawa

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

87 Scopus citations


Chronic inflammation contributes to a wide range of human diseases, and environments in infancy and childhood are important determinants of inflammatory phenotypes. The underlying biological mechanisms connecting early environments with the regulation of inflammation in adulthood are not known, but epigenetic processes are plausible candidates. We tested the hypothesis that patterns of DNA methylation (DNAm) in inflammatory genes in young adulthood would be predicted by early life nutritional, microbial, and psychosocial exposures previously associated with levels of inflammation. Data come from a populationbased longitudinal birth cohort study in metropolitan Cebu, the Philippines, and DNAm was characterized in whole blood samples from 494 participants (age 20-22 y). Analyses focused on probes in 114 target genes involved in the regulation of inflammation, and we identified 10 sites across nine genes where the level of DNAm was significantly predicted by the following variables: Household socioeconomic status in childhood, extended absence of a parent in childhood, exposure to animal feces in infancy, birth in the dry season, or duration of exclusive breastfeeding. To evaluate the biological significance of these sites, we tested for associations with a panel of inflammatory biomarkers measured in plasma obtained at the same age as DNAm assessment. Three sites predicted elevated inflammation, and one site predicted lower inflammation, consistent with the interpretation that levels of DNAm at these sites are functionally relevant. This pattern of results points toward DNAm as a potentially important biological mechanism through which developmental environments shape inflammatory phenotypes across the life course.

Original languageEnglish (US)
Pages (from-to)7611-7616
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number29
StatePublished - Jul 18 2017


  • Developmental origins of disease
  • Developmental origins of health
  • Ecological immunology
  • Epigenetics
  • Inflammation

ASJC Scopus subject areas

  • General


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