Houtepen, LC and Vinkers, CH and Carrillo-Roa, T and Hiemstra, M and van Lier, PA and Meeus, W and Branje, S and Heim, CM and Nemeroff, CB and Mill, J and Schalkwyk, LC and Creyghton, MP and Kahn, RS and Jo�ls, M and Binder, EB and Boks, MPM (2016) 'Genome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans.' Nature Communications, 7 (1). creators-Schalkwyk=3ALeonard_C=3A=3A. ISSN 2041-1723

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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.

Item Type:	Article
Uncontrolled Keywords:	Humans; Wounds and Injuries; Hydrocortisone; Histones; Stem Cell Factor; Stress, Psychological; Age Factors; DNA Methylation; Epigenesis, Genetic; Genome, Human; Models, Genetic; Adolescent; Adult; Aged; Middle Aged; Child; Female; Male; Gene Regulatory Networks; Genome-Wide Association Study; Young Adult; Genetic Loci; Ethnicity
Subjects:	Q Science > QH Natural history > QH301 Biology R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions:	Faculty of Science and Health Faculty of Science and Health > Life Sciences, School of
SWORD Depositor:	Elements
Depositing User:	Elements
Date Deposited:	18 Apr 2016 12:18
Last Modified:	07 Jan 2022 10:52
URI:	http://repository.essex.ac.uk/id/eprint/16406

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