Abstract
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.
Methods:
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.
Results:
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.
Conclusions:
Taken together, the study findings describe a novel epigenetic mechanism that helps explain how psychosocial stress exposure influences adolescent substance abuse.
| Original language | English |
|---|---|
| Journal | American Journal of Psychiatry |
| Early online date | 11 Dec 2018 |
| DOIs | |
| Publication status | E-pub ahead of print - 11 Dec 2018 |
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In: American Journal of Psychiatry, 11.12.2018.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Allele-Specific Methylation of SPDEF
T2 - A Novel Moderator of Psychosocial Stress and Substance Abuse
AU - Tay, Nicole Xi Hui
AU - Schumann, Gunter
AU - Macare, Christine
AU - Ruggeri, Barbara
AU - Jia, Tianye
AU - Chu, Congying
AU - Biondo, Francesca
AU - Ing, Alex James
AU - Luo, Qiang
AU - Sarkisyan, Daniil
AU - Banaschewski, Tobias
AU - Barker, Gareth John
AU - Bokde, Arun
AU - Bromberg, Uli
AU - Buchel, Christian
AU - Quinlan, Erin Burke
AU - Desrivieres, Sylvane
AU - Flor, Herta
AU - Frouin, V
AU - Garavan, Hugh
AU - Gowland, Penny
AU - Heinz, A
AU - Ittermann, Bernd
AU - Martinot, Jean-Luc
AU - Artiges, Eric
AU - Nees, Frauke
AU - Papadopoulos, Dimitri
AU - Paus, Tomáš
AU - Poustka, Luise
AU - Hohmann, Sarah
AU - Fröhner, Juliane H.
AU - Smolka, Michael N.
AU - Walter, Henrik
AU - Whelan, Robert
AU - Frieling, Helge
AU - Bleich, S.
AU - Barker, Edward
AU - Syvanen, Ann-Christine
AU - Ekstrom, Tomas J.
AU - Bakalkin, Georgy
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PY - 2018/12/11
Y1 - 2018/12/11
N2 - Objective: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.Methods: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.Results: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.Conclusions:Taken together, the study findings describe a novel epigenetic mechanism that helps explain how psychosocial stress exposure influences adolescent substance abuse.
AB - Objective: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.Methods: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.Results: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.Conclusions:Taken together, the study findings describe a novel epigenetic mechanism that helps explain how psychosocial stress exposure influences adolescent substance abuse.
U2 - 10.1176/appi.ajp.2018.17121360
DO - 10.1176/appi.ajp.2018.17121360
M3 - Article
SN - 0002-953X
JO - American Journal of Psychiatry
JF - American Journal of Psychiatry
ER -