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

Lotte C. Houtepen (), Christiaan H. Vinkers, Tania Carrillo-Roa, Marieke Hiemstra, Pol A. van Lier, Wim Meeus, Susan Branje, Christine M. Heim, Charles B. Nemeroff, Jonathan Mill, Leonard C. Schalkwyk, Menno P. Creyghton, René S. Kahn, Marian Joëls, Elisabeth B. Binder and Marco P. M. Boks ()
Additional contact information
Lotte C. Houtepen: Brain Center Rudolf Magnus, University Medical Center Utrecht
Christiaan H. Vinkers: Brain Center Rudolf Magnus, University Medical Center Utrecht
Tania Carrillo-Roa: Max Planck Institute of Psychiatry
Marieke Hiemstra: Research Centre Adolescent Development, University Utrecht (UU)
Pol A. van Lier: VU University
Wim Meeus: Research Centre Adolescent Development, University Utrecht (UU)
Susan Branje: Research Centre Adolescent Development, University Utrecht (UU)
Christine M. Heim: Institute of Medical Psychology, Charité-University Medicine, Medical Centre, 10117
Charles B. Nemeroff: Leonard M. Miller School of Medicine, University of Miami
Jonathan Mill: University of Exeter Medical School, University of Exeter
Leonard C. Schalkwyk: School of Biological Sciences, University of Essex
Menno P. Creyghton: Hubrecht Institute-KNAW and University Medical Center Utrecht (UMCU)
René S. Kahn: Brain Center Rudolf Magnus, University Medical Center Utrecht
Marian Joëls: Brain Center Rudolf Magnus, University Medical Center Utrecht (UMCU)
Elisabeth B. Binder: Max Planck Institute of Psychiatry
Marco P. M. Boks: Brain Center Rudolf Magnus, University Medical Center Utrecht

Nature Communications, 2016, vol. 7, issue 1, 1-10

Abstract: 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.

Date: 2016
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/ncomms10967 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10967

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms10967

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().