Format

Send to

Choose Destination
Nat Commun. 2016 Mar 21;7:10967. doi: 10.1038/ncomms10967.

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

Author information

1
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands.
2
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich 80804, Germany.
3
Research Centre Adolescent Development, Department Youth &Family, University Utrecht (UU), Utrecht 3584 CS, The Netherlands.
4
Department of Developmental Psychology, VU University, Amsterdam 1081 BT, The Netherlands.
5
Department of Developmental Psychology, Tilburg University 5000 LE, Tilburg, The Netherlands.
6
Institute of Medical Psychology, Charité-University Medicine, Medical Centre, 10117 Berlin, Germany.
7
Department of Biobehavioral Health, Pennsylvania State University, University Park, PA 16802, USA.
8
Department of Psychiatry and Behavioral Sciences, Leonard M. Miller School of Medicine, University of Miami, Miami, 33136, Florida, USA.
9
University of Exeter Medical School, University of Exeter, EX2 5DW, Devon, UK.
10
Institute of Psychiatry, Psychology &Neuroscience, King's College London, SE5 8AF, London, UK.
11
School of Biological Sciences, University of Essex, CO4 3SQ Colchester, UK.
12
Hubrecht Institute-KNAW and University Medical Center Utrecht (UMCU), Utrecht 3584CT, The Netherlands.
13
Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht (UMCU), Utrecht 3584 CG, The Netherlands.
14
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30329, USA.

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.

PMID:
26997371
PMCID:
PMC4802173
DOI:
10.1038/ncomms10967
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center