Allele-Specific Methylation of SPDEF: A Novel Moderator of Psychosocial Stress and Substance Abuse.
Adolescent
Alcohol Drinking
/ genetics
Alleles
DNA Methylation
Epigenesis, Genetic
Female
Gray Matter
/ diagnostic imaging
Humans
Male
Occipital Lobe
/ diagnostic imaging
Organ Size
Proto-Oncogene Proteins c-ets
/ genetics
Stress, Psychological
/ genetics
Substance-Related Disorders
/ genetics
Tobacco Use
/ genetics
Underage Drinking
Adolescents
Epigenetics
Stress
Substance Use
Journal
The American journal of psychiatry
ISSN: 1535-7228
Titre abrégé: Am J Psychiatry
Pays: United States
ID NLM: 0370512
Informations de publication
Date de publication:
01 02 2019
01 02 2019
Historique:
pubmed:
12
12
2018
medline:
22
11
2019
entrez:
12
12
2018
Statut:
ppublish
Résumé
Psychosocial stress is a key risk factor for substance abuse among adolescents. Recently, epigenetic processes such as DNA methylation have emerged as potential mechanisms that could mediate this relationship. The authors conducted a genome-wide methylation analysis to investigate whether differentially methylated regions are associated with psychosocial stress in an adolescent population. A methylome-wide analysis of differentially methylated regions was used to examine a sample of 1,287 14-year-old adolescents (50.7% of them female) from the European IMAGEN study. The Illumina 450k array was used to assess DNA methylation, pyrosequencing was used for technical replication, and linear regression analyses were used to identify associations with psychosocial stress and substance use (alcohol and tobacco). Findings were replicated by pyrosequencing a test sample of 413 participants from the IMAGEN study. Hypermethylation in the sterile alpha motif/pointed domain containing the ETS transcription factor (SPDEF) gene locus was associated with a greater number of stressful life events in an allele-dependent way. Among individuals with the minor G-allele, SPDEF methylation moderated the association between psychosocial stress and substance abuse. SPDEF methylation interacted with lifetime stress in gray matter volume in the right cuneus, which in turn was associated with the frequency of alcohol and tobacco use. SPDEF was involved in the regulation of trans-genes linked to substance use. Taken together, the study findings describe a novel epigenetic mechanism that helps explain how psychosocial stress exposure influences adolescent substance abuse.
Identifiants
pubmed: 30525907
doi: 10.1176/appi.ajp.2018.17121360
doi:
Substances chimiques
Proto-Oncogene Proteins c-ets
0
SPDEF protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
146-155Subventions
Organisme : Medical Research Council
ID : MR/N000390/1
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : R01 MH085772
Pays : United States
Organisme : NIBIB NIH HHS
ID : U54 EB020403
Pays : United States
Commentaires et corrections
Type : CommentIn