Internationally adopted adolescents who are adopted as young children from conditions of poverty and deprivation have poorer physical and mental health outcomes than do adolescents conceived, born, and raised in the United States by families similar to those who adopt internationally. Using a sample of Russian and Eastern European adoptees to control for Caucasian race and US birth, and nonadopted offspring of well-educated and well-resourced parents to control for postadoption conditions, we hypothesized that the important differences in environments, conception to adoption, might be reflected in epigenetic patterns between groups, specifically in DNA methylation. Thus, we conducted an epigenome-wide association study to compare DNA methylation profiles at approximately 416,000 individual CpG loci from peripheral blood mononuclear cells of 50 adopted youth and 33 nonadopted youth. Adopted youth averaged 22 months at adoption, and both groups averaged 15 years at testing; thus, roughly 80% of their lives were lived in similar circumstances. Although concurrent physical health did not differ, cell-type composition predicted using the DNA methylation data revealed a striking difference in the white blood cell-type composition of the adopted and nonadopted youth. After correcting for cell type and removing invariant probes, 30 CpG sites in 19 genes were more methylated in the adopted group. We also used an exploratory functional analysis that revealed that 223 gene ontology terms, clustered in neural and developmental categories, were significantly enriched between groups.
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We thank the families and youth who participated in this study and Bonny Donzella, Tori Simenec, Natalie Ottum, and Zamzam Ahmed for their assistance with data collection. We are especially grateful to Elena Grigorenko, Oksana Naumova, and their coauthors, who graciously shared their data. This work was supported by funds from the Child and Brain Development Program of the Canadian Institute for Advanced Research (to M.R.G. and M.S.K.), the Interdisciplinary Training Program in Cognitive Science (Grant T32 HD007151 to E.A.E.), an NIMH Training Grant Fellowship (T32MH015755 to J.R.D.), a Mining for Miracles fellowship from the Child and Family Research Institute (to M.J.J.), and the Canada Research Chair in Social Epigenetics (to M.S.K.). The research reported here was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health