TY  - JOUR
PY  - 2018//
TI  - Epigenetic changes in the CRH gene are related to severity of suicide attempt and a general psychiatric risk score in adolescents
JO  - EBioMedicine
A1  - Jokinen, Jussi
A1  - Boström, Adrian E.
A1  - Dadfar, Ali
A1  - Ciuculete, Diana M.
A1  - Chatzittofis, Andreas
A1  - Åsberg, Marie
A1  - Schiöth, Helgi B.
SP  - 123
EP  - 133
VL  - 27
IS  - 
N2  - The aim of this study, comprising 88 suicide attempters, was to identify hypothalamic-pituitary-adrenal (HPA) -axis coupled CpG-sites showing methylation shifts linked to severity of the suicide attempt. Candidate methylation loci were further investigated as risk loci for a general psychiatric risk score in two cohorts of adolescents (cohort 1 and 2). The genome-wide methylation pattern was measured in whole blood using the Illumina Infinium Methylation EPIC BeadChip. Subjects were stratified into high-risk and low-risk groups based on the severity of the suicidal behavior. We included CpG sites located within 2000 basepairs away from transcriptional start site of the following HPA-axis coupled genes: corticotropin releasing hormone (CRH), corticotropin releasing hormone binding protein (CRHBP), corticotropin releasing hormone receptor 1 (CRHR1), corticotropin releasing hormone receptor 2 (CRHR2), FK506-binding protein 51 (FKBP5) and the glucocorticoid receptor (NR3C1). The methylation state of two corticotropin releasing hormone (CRH)-associated CpG sites were significantly hypomethylated in the high-risk group of suicide attempters (n=31) (cg19035496 and cg23409074) (p<0.001). Adolescent cohort 1 and 2 consisted of 129 and 93 subjects, respectively, and were stratified by the in silico generated DAWBA measurements of a general psychiatric risk score into high-risk group (>~50% risk) or controls. In adolescent cohort 2, cg19035496 was hypermethylated in subjects with a high general psychiatric risk score. Our results show epigenetic changes in the CRH gene related to severity of suicide attempt in adults and a general psychiatric risk score in adolescents.<br><br>Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.<p />  <p>Language: en</p>
LA  - en
SN  - 2352-3964
UR  - http://dx.doi.org/10.1016/j.ebiom.2017.12.018
ID  - ref1
ER  -