The mediating role of KITLG DNA methylation in the association between childhood adversity and cortisol stress reactivity does not replicate in monocytes

Leonard Frach; Sascha Tierling; Marion Schwaiger; Dirk Moser; Markus Heinrichs; Jan G Hengstler; Jörn Walter; Robert Kumsta

doi:10.1016/j.psyneuen.2020.104653

The mediating role of KITLG DNA methylation in the association between childhood adversity and cortisol stress reactivity does not replicate in monocytes

Psychoneuroendocrinology. 2020 Jun:116:104653. doi: 10.1016/j.psyneuen.2020.104653. Epub 2020 Mar 20.

Authors

Leonard Frach¹, Sascha Tierling², Marion Schwaiger¹, Dirk Moser¹, Markus Heinrichs³, Jan G Hengstler⁴, Jörn Walter², Robert Kumsta⁵

Affiliations

¹ Department of Genetic Psychology, Faculty of Psychology, Ruhr University Bochum, Bochum, Germany.
² Department of Genetics/ Epigenetics, Saarland University, Saarbrücken, Germany.
³ Department of Psychology, Laboratory for Biological and Personality Psychology, University of Freiburg, Freiburg, Germany; Freiburg Brain Imaging Center, University Medical Center, University of Freiburg, Freiburg, Germany.
⁴ Leibniz Research Centre for Working Environment and Human Factors at the Technical University of Dortmund (IfADo), Dortmund, Germany.
⁵ Department of Genetic Psychology, Faculty of Psychology, Ruhr University Bochum, Bochum, Germany. Electronic address: robert.kumsta@rub.de.

PMID: 32203862
DOI: 10.1016/j.psyneuen.2020.104653

Abstract

Adverse childhood experiences such as maltreatment or neglect are associated with mental health problems in adulthood. Changes in the regulation of the psychological and physiological stress reaction, mediated via epigenetic modifications, are discussed as potential mechanisms. This study aimed to replicate the role of DNA methylation of the KITLG gene in mediating the association between childhood adversity and stress-induced cortisol reactivity in a sample of adults reporting childhood adversity and a matched control group (N = 60). DNA was extracted from purified CD14⁺ monocytes and genome-wide DNA methylation was assessed with the 450k BeadChip for targeted replication and exploratory analyses. As previously reported, childhood adversity was associated with significantly lower cortisol reactivity to stress. We could neither replicate the association between KITLG DNA methylation and cortisol stress reactivity nor the association with childhood adversity. Moreover, DNA methylation of the target CpG (cg27512205) was not associated with KITLG mRNA expression in monocytes. Exploratory analyses of array-wide DNA methylation patterns showed no significant results for individual sites after correction for multiple testing - neither in association with childhood trauma nor with adult cortisol stress reactivity. The analysis of differentially methylated regions (DMRs) revealed two significant regions which both mapped to non-coding genes in the association with cortisol stress reactivity. The mediating role of DNA methylation of the KITLG locus in the association between childhood adversity and cortisol stress reactivity could not be replicated in monocytes. In addition to differences in investigated tissue, reasons for non-replication might include differences between samples in age, ethnicity, trauma severity, and cortisol reactivity.

Keywords: Childhood adversity; DNA methylation; EWAS; Replication; Stress; TSST.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Adverse Childhood Experiences*
Aged
DNA Methylation / physiology*
Epigenesis, Genetic / physiology
Female
Humans
Hydrocortisone / metabolism*
Male
Middle Aged
Monocytes / metabolism*
Stem Cell Factor / genetics
Stem Cell Factor / metabolism*
Stress, Psychological / metabolism*

Substances

KITLG protein, human
Stem Cell Factor
Hydrocortisone