Association between DNA methylation of the KITLG gene and cortisol levels under stress: a replication study

Jo Wrigglesworth, Marie-Laure Ancelin, Karen Ritchie, Joanne Ryan

Research output: Contribution to journalArticleResearchpeer-review

Abstract

A recent study reported for the first time, that DNA methylation of the KITLG gene mediates the association between childhood trauma and cortisol stress reactivity. Our study aimed to provide the first independent replication of these findings. ESPRIT is a prospective study of community-dwelling participants (age ≥ 65), randomly selected from the electoral rolls of the Montpellier district, in France. Clinical depression was assessed using the Mini-International Neuropsychiatric Interview (MINI, French version 5.00), and the Centre for Epidemiological Studies Depression Scale (CES-D). Experiences of childhood adversity were ascertained via a 25-item questionnaire. Morning, evening, and diurnal salivary cortisol was measured under basal and stress conditions and determined using direct radioimmunoassay analysis. DNA methylation of the KITLG gene was quantified in whole blood using the SEQUENOM MassARRAY EpiTYPER platform. A significant negative association was observed between KITLG DNA methylation and both morning cortisol (β = −1.846 ± 0.666, p =.007) and diurnal cortisol (area under curve [AUC]) (β = −19.429 ± 8.868, p =.031) under a stress condition. However, only the former association was significant after correcting for multiple testing. Further, this association remained after adjusting for age, sex, and depression status. No significant association was observed between childhood trauma and KITLG DNA methylation in this older population. This study provides support for an association between KITLG methylation and stress cortisol levels, suggesting that DNA methylation of this gene may play a role in the longer term regulation of the stress system.Lay summary   The significant negative association between KITLG DNA methylation and morning cortisol, measured under a stressful condition, suggests that individuals with higher KITLG methylation will secrete lower levels of cortisol whilst under stress.

Original languageEnglish
Pages (from-to)162-168
Number of pages7
JournalStress-The International Journal on the Biology of Stress
Volume22
Issue number1
DOIs
Publication statusPublished - 2 Jan 2019

Keywords

  • cortisol
  • DNA methylation
  • epigenetics
  • hypothalamic pituitary adrenal axis
  • KITLG
  • stress response

Cite this

@article{e42c62cd109d4732bb575320a42dc173,
title = "Association between DNA methylation of the KITLG gene and cortisol levels under stress: a replication study",
abstract = "A recent study reported for the first time, that DNA methylation of the KITLG gene mediates the association between childhood trauma and cortisol stress reactivity. Our study aimed to provide the first independent replication of these findings. ESPRIT is a prospective study of community-dwelling participants (age ≥ 65), randomly selected from the electoral rolls of the Montpellier district, in France. Clinical depression was assessed using the Mini-International Neuropsychiatric Interview (MINI, French version 5.00), and the Centre for Epidemiological Studies Depression Scale (CES-D). Experiences of childhood adversity were ascertained via a 25-item questionnaire. Morning, evening, and diurnal salivary cortisol was measured under basal and stress conditions and determined using direct radioimmunoassay analysis. DNA methylation of the KITLG gene was quantified in whole blood using the SEQUENOM MassARRAY EpiTYPER platform. A significant negative association was observed between KITLG DNA methylation and both morning cortisol (β = −1.846 ± 0.666, p =.007) and diurnal cortisol (area under curve [AUC]) (β = −19.429 ± 8.868, p =.031) under a stress condition. However, only the former association was significant after correcting for multiple testing. Further, this association remained after adjusting for age, sex, and depression status. No significant association was observed between childhood trauma and KITLG DNA methylation in this older population. This study provides support for an association between KITLG methylation and stress cortisol levels, suggesting that DNA methylation of this gene may play a role in the longer term regulation of the stress system.Lay summary   The significant negative association between KITLG DNA methylation and morning cortisol, measured under a stressful condition, suggests that individuals with higher KITLG methylation will secrete lower levels of cortisol whilst under stress.",
keywords = "cortisol, DNA methylation, epigenetics, hypothalamic pituitary adrenal axis, KITLG, stress response",
author = "Jo Wrigglesworth and Marie-Laure Ancelin and Karen Ritchie and Joanne Ryan",
year = "2019",
month = "1",
day = "2",
doi = "10.1080/10253890.2018.1519019",
language = "English",
volume = "22",
pages = "162--168",
journal = "Stress-The International Journal on the Biology of Stress",
issn = "1025-3890",
publisher = "Taylor & Francis",
number = "1",

}

Association between DNA methylation of the KITLG gene and cortisol levels under stress : a replication study. / Wrigglesworth, Jo; Ancelin, Marie-Laure; Ritchie, Karen; Ryan, Joanne.

In: Stress-The International Journal on the Biology of Stress, Vol. 22, No. 1, 02.01.2019, p. 162-168.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Association between DNA methylation of the KITLG gene and cortisol levels under stress

T2 - a replication study

AU - Wrigglesworth, Jo

AU - Ancelin, Marie-Laure

AU - Ritchie, Karen

AU - Ryan, Joanne

PY - 2019/1/2

Y1 - 2019/1/2

N2 - A recent study reported for the first time, that DNA methylation of the KITLG gene mediates the association between childhood trauma and cortisol stress reactivity. Our study aimed to provide the first independent replication of these findings. ESPRIT is a prospective study of community-dwelling participants (age ≥ 65), randomly selected from the electoral rolls of the Montpellier district, in France. Clinical depression was assessed using the Mini-International Neuropsychiatric Interview (MINI, French version 5.00), and the Centre for Epidemiological Studies Depression Scale (CES-D). Experiences of childhood adversity were ascertained via a 25-item questionnaire. Morning, evening, and diurnal salivary cortisol was measured under basal and stress conditions and determined using direct radioimmunoassay analysis. DNA methylation of the KITLG gene was quantified in whole blood using the SEQUENOM MassARRAY EpiTYPER platform. A significant negative association was observed between KITLG DNA methylation and both morning cortisol (β = −1.846 ± 0.666, p =.007) and diurnal cortisol (area under curve [AUC]) (β = −19.429 ± 8.868, p =.031) under a stress condition. However, only the former association was significant after correcting for multiple testing. Further, this association remained after adjusting for age, sex, and depression status. No significant association was observed between childhood trauma and KITLG DNA methylation in this older population. This study provides support for an association between KITLG methylation and stress cortisol levels, suggesting that DNA methylation of this gene may play a role in the longer term regulation of the stress system.Lay summary   The significant negative association between KITLG DNA methylation and morning cortisol, measured under a stressful condition, suggests that individuals with higher KITLG methylation will secrete lower levels of cortisol whilst under stress.

AB - A recent study reported for the first time, that DNA methylation of the KITLG gene mediates the association between childhood trauma and cortisol stress reactivity. Our study aimed to provide the first independent replication of these findings. ESPRIT is a prospective study of community-dwelling participants (age ≥ 65), randomly selected from the electoral rolls of the Montpellier district, in France. Clinical depression was assessed using the Mini-International Neuropsychiatric Interview (MINI, French version 5.00), and the Centre for Epidemiological Studies Depression Scale (CES-D). Experiences of childhood adversity were ascertained via a 25-item questionnaire. Morning, evening, and diurnal salivary cortisol was measured under basal and stress conditions and determined using direct radioimmunoassay analysis. DNA methylation of the KITLG gene was quantified in whole blood using the SEQUENOM MassARRAY EpiTYPER platform. A significant negative association was observed between KITLG DNA methylation and both morning cortisol (β = −1.846 ± 0.666, p =.007) and diurnal cortisol (area under curve [AUC]) (β = −19.429 ± 8.868, p =.031) under a stress condition. However, only the former association was significant after correcting for multiple testing. Further, this association remained after adjusting for age, sex, and depression status. No significant association was observed between childhood trauma and KITLG DNA methylation in this older population. This study provides support for an association between KITLG methylation and stress cortisol levels, suggesting that DNA methylation of this gene may play a role in the longer term regulation of the stress system.Lay summary   The significant negative association between KITLG DNA methylation and morning cortisol, measured under a stressful condition, suggests that individuals with higher KITLG methylation will secrete lower levels of cortisol whilst under stress.

KW - cortisol

KW - DNA methylation

KW - epigenetics

KW - hypothalamic pituitary adrenal axis

KW - KITLG

KW - stress response

UR - http://www.scopus.com/inward/record.url?scp=85054709178&partnerID=8YFLogxK

U2 - 10.1080/10253890.2018.1519019

DO - 10.1080/10253890.2018.1519019

M3 - Article

VL - 22

SP - 162

EP - 168

JO - Stress-The International Journal on the Biology of Stress

JF - Stress-The International Journal on the Biology of Stress

SN - 1025-3890

IS - 1

ER -