The mediating role of KITLG DNA methylation in the association between childhood adversity and cortisol stress reactivity does not replicate in monocytes
Journal article
Frach, Leonard, Tierling, Sascha, Schwaiger, Marion, Moser, Dirk, Heinrichs, Markus, Hengstler, Jan G., Walter, Jörn and Kumsta, Robert. (2020). The mediating role of KITLG DNA methylation in the association between childhood adversity and cortisol stress reactivity does not replicate in monocytes. Psychoneuroendocrinology. 116, p. 104653. https://doi.org/10.1016/j.psyneuen.2020.104653
Authors | Frach, Leonard, Tierling, Sascha, Schwaiger, Marion, Moser, Dirk, Heinrichs, Markus, Hengstler, Jan G., Walter, Jörn and Kumsta, Robert |
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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 | DNA methylation; childhood adversity; EWAS; stress; TSST; replication |
Year | 2020 |
Journal | Psychoneuroendocrinology |
Journal citation | 116, p. 104653 |
Publisher | Elsevier Ltd |
ISSN | 0306-4530 |
Digital Object Identifier (DOI) | https://doi.org/10.1016/j.psyneuen.2020.104653 |
Scopus EID | 2-s2.0-85081904246 |
Research or scholarly | Research |
Page range | 1-7 |
Publisher's version | License All rights reserved File Access Level Controlled |
Output status | Published |
Publication dates | |
Online | 20 Mar 2020 |
Publication process dates | |
Accepted | 09 Mar 2020 |
Deposited | 15 Jul 2021 |
https://acuresearchbank.acu.edu.au/item/8w5zy/the-mediating-role-of-kitlg-dna-methylation-in-the-association-between-childhood-adversity-and-cortisol-stress-reactivity-does-not-replicate-in-monocytes
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