%0 Journal Article %A Shan Jiang %A Noriko Kamei %A Jessica L. Bolton %A Xinyi Ma %A Hal S. Stern %A Tallie Z. Baram %A Ali Mortazavi %T Intra-individual methylomics detects the impact of early-life adversity %D 2018 %R 10.1101/440503 %J bioRxiv %P 440503 %X Genetic and environmental factors interact during sensitive periods early in life to influence mental health and disease. These influences involve modulating the function of neurons and neuronal networks via epigenetic processes such as DNA methylation. However, it is not known if DNA methylation changes outside the brain provide an ‘epigenetic signature’ of early-life experiences in an individual child that may serve as a marker for vulnerability or resilience to mental illness. Here, to obviate the massive variance among individuals, we employed a novel intra-individual approach by testing DNA methylation from buccal cells of individual rats before and immediately after exposure to one week of typical or adverse life experience. We show that whereas inter-individual changes in DNA methylation reflect the effect of age, DNA methylation changes within paired DNA samples from the same individual reflect the impact of diverse neonatal experiences on the individual. The methylome signature of early-life experience is enriched in genes encoding transcription factors and key molecular cellular pathways. Specifically, genes involved in cell morphogenesis and differentiation were more methylated in pups exposed to the adverse environment whereas pathways of response to injury and stress were less methylated. Thus, intra-individual methylome signatures indicate large-scale transcription-driven alterations of cellular fate, growth and function. Our observations in rats--that distinct early-life experiences generate specific individual methylome signatures in accessible peripheral cells--should be readily testable in humans. %U https://www.biorxiv.org/content/biorxiv/early/2018/10/11/440503.full.pdf