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dc.contributor.authorKumsta, R
dc.contributor.authorMarzi, SJ
dc.contributor.authorViana, J
dc.contributor.authorDempster, EL
dc.contributor.authorCrawford, B
dc.contributor.authorRutter, M
dc.contributor.authorMill, J
dc.contributor.authorSonuga-Barke, EJ
dc.date.accessioned2017-03-14T09:50:55Z
dc.date.issued2016-06-07
dc.description.abstractExposure to adverse rearing environments including institutional deprivation and severe childhood abuse is associated with an increased risk for mental and physical health problems across the lifespan. Although the mechanisms mediating these effects are not known, recent work in rodent models suggests that epigenetic processes may be involved. We studied the impact of severe early-life adversity on epigenetic variation in a sample of adolescents adopted from the severely depriving orphanages of the Romanian communist era in the 1980s. We quantified buccal cell DNA methylation at ~400 000 sites across the genome in Romanian adoptees exposed to either extended (6-43 months; n=16) or limited duration (<6 months; n=17) of severe early-life deprivation, in addition to a matched sample of UK adoptees (n=16) not exposed to severe deprivation. Although no probe-wise differences remained significant after controlling for the number of probes tested, we identified an exposure-associated differentially methylated region (DMR) spanning nine sequential CpG sites in the promoter-regulatory region of the cytochrome P450 2E1 gene (CYP2E1) on chromosome 10 (corrected P=2.98 × 10(-5)). Elevated DNA methylation across this region was also associated with deprivation-related clinical markers of impaired social cognition. Our data suggest that environmental insults of sufficient biological impact during early development are associated with long-lasting epigenetic changes, potentially reflecting a biological mechanism linking the effects of early-life adversity to cognitive and neurobiological phenotypes.en_GB
dc.description.sponsorshipThe current ERA study is supported by ESRC grant ES/I037970/1 and MRC grant MR/K022474/1 to EJSS-B. RK acknowledges grant support from the Deutsche Forschungsgemeinschaft (DFG, KU 2479/3-1, KU 2479/3-2). SJM is funded by the EU-FP7 Marie Curie ITN EpiTrain (REA grant agreement no. 316758).en_GB
dc.identifier.citationVol. 6, e830 -en_GB
dc.identifier.doi10.1038/tp.2016.95
dc.identifier.othertp201695
dc.identifier.urihttp://hdl.handle.net/10871/26544
dc.language.isoenen_GB
dc.publisherNature Publishing Groupen_GB
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/27271856en_GB
dc.rightsThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.en_GB
dc.titleSevere psychosocial deprivation in early childhood is associated with increased DNA methylation across a region spanning the transcription start site of CYP2E1.en_GB
dc.typeArticleen_GB
dc.date.available2017-03-14T09:50:55Z
exeter.place-of-publicationUnited Statesen_GB
dc.descriptionPublished onlineen_GB
dc.descriptionJournal Articleen_GB
dc.descriptionThis is the final version of the article. Available from Nature Publishing Group via the DOI in this record.en_GB
dc.identifier.eissn2158-3188
dc.identifier.journalTranslational Psychiatryen_GB


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