IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms10967.html
   My bibliography  Save this article

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

Author

Listed:
  • 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)
    Tilburg University 5000 LE)

  • Susan Branje

    (Research Centre Adolescent Development, University Utrecht (UU))

  • Christine M. Heim

    (Institute of Medical Psychology, Charité-University Medicine, Medical Centre, 10117
    Pennsylvania State University, University Park)

  • Charles B. Nemeroff

    (Leonard M. Miller School of Medicine, University of Miami)

  • Jonathan Mill

    (University of Exeter Medical School, University of Exeter
    Institute of Psychiatry, Psychology & Neuroscience, King's College London)

  • 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
    Emory University School of Medicine)

  • Marco P. M. Boks

    (Brain Center Rudolf Magnus, University Medical Center Utrecht)

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.

Suggested Citation

  • 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. Sc, 2016. "Genome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans," Nature Communications, Nature, vol. 7(1), pages 1-10, April.
  • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10967
    DOI: 10.1038/ncomms10967
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms10967
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/ncomms10967?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Kobe Ridder & Huiwen Che & Kaat Leroy & Bernard Thienpont, 2024. "Benchmarking of methods for DNA methylome deconvolution," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Laurens Holmes & Emily Shutman & Chinacherem Chinaka & Kerti Deepika & Lavisha Pelaez & Kirk W. Dabney, 2019. "Aberrant Epigenomic Modulation of Glucocorticoid Receptor Gene (NR3C1) in Early Life Stress and Major Depressive Disorder Correlation: Systematic Review and Quantitative Evidence Synthesis," IJERPH, MDPI, vol. 16(21), pages 1-17, November.
    3. Conching, Andie Kealohi Sato & Thayer, Zaneta, 2019. "Biological pathways for historical trauma to affect health: A conceptual model focusing on epigenetic modifications," Social Science & Medicine, Elsevier, vol. 230(C), pages 74-82.
    4. Cai, Xizhen & Zhu, Yeying & Huang, Yuan & Ghosh, Debashis, 2022. "High-dimensional causal mediation analysis based on partial linear structural equation models," Computational Statistics & Data Analysis, Elsevier, vol. 174(C).

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10967. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.