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, Marco P.M. Boks

Research output: Contribution to journalArticlepeer-review

126 Scopus citations


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.

Original languageEnglish (US)
Article number10967
JournalNature communications
StatePublished - Mar 21 2016

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


Dive into the research topics of 'Genome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans'. Together they form a unique fingerprint.

Cite this