Genome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans.

2.50
Hdl Handle:
http://hdl.handle.net/11287/620269
Title:
Genome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans.
Authors:
Houtepen, L. C.; Vinkers, C. H.; Carrillo-Roa, T.; Hiemstra, M.; van Lier, P. A.; Meeus, W.; Branje, S.; Heim, C. M.; Nemeroff, C. B.; Mill, Jonathan; Schalkwyk, L. C.; Creyghton, M. P.; Kahn, R. S.; Joëls, M.; Binder, E. B.; Boks, M. P. M.
Abstract:
DNA methylation likely plays a role in the regulation of human stress reactivity. Here we show that in a genome-wide analysis of blood DNA methylation in 85 healthy individuals, a locus in the Kit ligand gene (KITLG; cg27512205) showed the strongest association with cortisol stress reactivity (P=5.8 × 10(-6)). Replication was obtained in two independent samples using either blood (N=45, P=0.001) or buccal cells (N=255, P=0.004). KITLG methylation strongly mediates the relationship between childhood trauma and cortisol stress reactivity in the discovery sample (32% mediation). Its genomic location, a CpG island shore within an H3K27ac enhancer mark, and the correlation between methylation in the blood and prefrontal cortex provide further evidence that KITLG methylation is functionally relevant for the programming of stress reactivity in the human brain. Our results extend preclinical evidence for epigenetic regulation of stress reactivity to humans and provide leads to enhance our understanding of the neurobiological pathways underlying stress vulnerability.
Citation:
Genome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans. 2016, 7:10967 Nat Commun
Publisher:
Nature
Journal:
Nature communications
Issue Date:
21-Mar-2016
URI:
http://hdl.handle.net/11287/620269
DOI:
10.1038/ncomms10967
PubMed ID:
26997371
Additional Links:
http://dx.doi.org/10.1038/ncomms10967
Note:
This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site.
Type:
Journal Article
Language:
en
ISSN:
2041-1723
Appears in Collections:
Honorary contracts publications; 2016 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorHoutepen, L. C.en
dc.contributor.authorVinkers, C. H.en
dc.contributor.authorCarrillo-Roa, T.en
dc.contributor.authorHiemstra, M.en
dc.contributor.authorvan Lier, P. A.en
dc.contributor.authorMeeus, W.en
dc.contributor.authorBranje, S.en
dc.contributor.authorHeim, C. M.en
dc.contributor.authorNemeroff, C. B.en
dc.contributor.authorMill, Jonathanen
dc.contributor.authorSchalkwyk, L. C.en
dc.contributor.authorCreyghton, M. P.en
dc.contributor.authorKahn, R. S.en
dc.contributor.authorJoëls, M.en
dc.contributor.authorBinder, E. B.en
dc.contributor.authorBoks, M. P. M.en
dc.date.accessioned2017-03-13T09:55:24Z-
dc.date.available2017-03-13T09:55:24Z-
dc.date.issued2016-03-21-
dc.identifier.citationGenome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans. 2016, 7:10967 Nat Communen
dc.identifier.issn2041-1723-
dc.identifier.pmid26997371-
dc.identifier.doi10.1038/ncomms10967-
dc.identifier.urihttp://hdl.handle.net/11287/620269-
dc.description.abstractDNA methylation likely plays a role in the regulation of human stress reactivity. Here we show that in a genome-wide analysis of blood DNA methylation in 85 healthy individuals, a locus in the Kit ligand gene (KITLG; cg27512205) showed the strongest association with cortisol stress reactivity (P=5.8 × 10(-6)). Replication was obtained in two independent samples using either blood (N=45, P=0.001) or buccal cells (N=255, P=0.004). KITLG methylation strongly mediates the relationship between childhood trauma and cortisol stress reactivity in the discovery sample (32% mediation). Its genomic location, a CpG island shore within an H3K27ac enhancer mark, and the correlation between methylation in the blood and prefrontal cortex provide further evidence that KITLG methylation is functionally relevant for the programming of stress reactivity in the human brain. Our results extend preclinical evidence for epigenetic regulation of stress reactivity to humans and provide leads to enhance our understanding of the neurobiological pathways underlying stress vulnerability.en
dc.language.isoenen
dc.publisherNatureen
dc.relation.urlhttp://dx.doi.org/10.1038/ncomms10967en
dc.rightsArchived with thanks to Nature communicationsen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.titleGenome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans.en
dc.typeJournal Articleen
dc.identifier.journalNature communicationsen
dc.description.noteThis article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site.en
dc.type.versionPublisheden

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