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Allele-Specific Methylation of SPDEF: A Novel Moderator of Psychosocial Stress and Substance Abuse

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Allele-Specific Methylation of SPDEF: A Novel Moderator of Psychosocial Stress and Substance Abuse. / Tay, Nicole; Macare, Christine; Liu, Yun; Ruggeri, Barbara; Jia, Tianye; Chu, Congying; Biondo, Francesca; Ing, Alex; Luo, Qiang; Sarkysian, Daniil; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Bromberg, Uli; Büchel, Christian; Quinlan, Erin Burke; Desrivières, Sylvane; Flor, Herta; Frouin, Vincent; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Ittermann, Bernd; Martinot, Jean-Luc; Artiges, Eric; Nees, Frauke; Orfanos, Dimitri Papadopoulos; Paus, Tomáš; Poustka, Luise; Hohmann, Sarah; Fröhner, Juliane H; Smolka, Michael N; Walter, Henrik; Whelan, Robert; Frieling, Helge; Bleich, Stefan; Barker, Edward D; Syvänen, Ann-Christine; Rüegg, Joëlle; Ekström, Tomas J; Bakalkin, Georgy; Schumann, Gunter; IMAGEN Consortium.

In: AM J PSYCHIAT, Vol. 176, No. 2, 01.02.2019, p. 146-155.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Tay, N, Macare, C, Liu, Y, Ruggeri, B, Jia, T, Chu, C, Biondo, F, Ing, A, Luo, Q, Sarkysian, D, Banaschewski, T, Barker, GJ, Bokde, ALW, Bromberg, U, Büchel, C, Quinlan, EB, Desrivières, S, Flor, H, Frouin, V, Garavan, H, Gowland, P, Heinz, A, Ittermann, B, Martinot, J-L, Artiges, E, Nees, F, Orfanos, DP, Paus, T, Poustka, L, Hohmann, S, Fröhner, JH, Smolka, MN, Walter, H, Whelan, R, Frieling, H, Bleich, S, Barker, ED, Syvänen, A-C, Rüegg, J, Ekström, TJ, Bakalkin, G, Schumann, G & IMAGEN Consortium 2019, 'Allele-Specific Methylation of SPDEF: A Novel Moderator of Psychosocial Stress and Substance Abuse', AM J PSYCHIAT, vol. 176, no. 2, pp. 146-155. https://doi.org/10.1176/appi.ajp.2018.17121360

APA

Tay, N., Macare, C., Liu, Y., Ruggeri, B., Jia, T., Chu, C., Biondo, F., Ing, A., Luo, Q., Sarkysian, D., Banaschewski, T., Barker, G. J., Bokde, A. L. W., Bromberg, U., Büchel, C., Quinlan, E. B., Desrivières, S., Flor, H., Frouin, V., ... IMAGEN Consortium (2019). Allele-Specific Methylation of SPDEF: A Novel Moderator of Psychosocial Stress and Substance Abuse. AM J PSYCHIAT, 176(2), 146-155. https://doi.org/10.1176/appi.ajp.2018.17121360

Vancouver

Tay N, Macare C, Liu Y, Ruggeri B, Jia T, Chu C et al. Allele-Specific Methylation of SPDEF: A Novel Moderator of Psychosocial Stress and Substance Abuse. AM J PSYCHIAT. 2019 Feb 1;176(2):146-155. https://doi.org/10.1176/appi.ajp.2018.17121360

Bibtex

@article{f7317889809d4c539d15b80f8b97c363,
title = "Allele-Specific Methylation of SPDEF: A Novel Moderator of Psychosocial Stress and Substance Abuse",
abstract = "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.",
author = "Nicole Tay and Christine Macare and Yun Liu and Barbara Ruggeri and Tianye Jia and Congying Chu and Francesca Biondo and Alex Ing and Qiang Luo and Daniil Sarkysian and Tobias Banaschewski and Barker, {Gareth J} and Bokde, {Arun L W} and Uli Bromberg and Christian B{\"u}chel and Quinlan, {Erin Burke} and Sylvane Desrivi{\`e}res and Herta Flor and Vincent Frouin and Hugh Garavan and Penny Gowland and Andreas Heinz and Bernd Ittermann and Jean-Luc Martinot and Eric Artiges and Frauke Nees and Orfanos, {Dimitri Papadopoulos} and Tom{\'a}{\v s} Paus and Luise Poustka and Sarah Hohmann and Fr{\"o}hner, {Juliane H} and Smolka, {Michael N} and Henrik Walter and Robert Whelan and Helge Frieling and Stefan Bleich and Barker, {Edward D} and Ann-Christine Syv{\"a}nen and Jo{\"e}lle R{\"u}egg and Ekstr{\"o}m, {Tomas J} and Georgy Bakalkin and Gunter Schumann and {IMAGEN Consortium}",
year = "2019",
month = feb,
day = "1",
doi = "10.1176/appi.ajp.2018.17121360",
language = "English",
volume = "176",
pages = "146--155",
journal = "AM J PSYCHIAT",
issn = "0002-953X",
publisher = "American Psychiatric Association",
number = "2",

}

RIS

TY - JOUR

T1 - Allele-Specific Methylation of SPDEF: A Novel Moderator of Psychosocial Stress and Substance Abuse

AU - Tay, Nicole

AU - Macare, Christine

AU - Liu, Yun

AU - Ruggeri, Barbara

AU - Jia, Tianye

AU - Chu, Congying

AU - Biondo, Francesca

AU - Ing, Alex

AU - Luo, Qiang

AU - Sarkysian, Daniil

AU - Banaschewski, Tobias

AU - Barker, Gareth J

AU - Bokde, Arun L W

AU - Bromberg, Uli

AU - Büchel, Christian

AU - Quinlan, Erin Burke

AU - Desrivières, Sylvane

AU - Flor, Herta

AU - Frouin, Vincent

AU - Garavan, Hugh

AU - Gowland, Penny

AU - Heinz, Andreas

AU - Ittermann, Bernd

AU - Martinot, Jean-Luc

AU - Artiges, Eric

AU - Nees, Frauke

AU - Orfanos, Dimitri Papadopoulos

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, Stefan

AU - Barker, Edward D

AU - Syvänen, Ann-Christine

AU - Rüegg, Joëlle

AU - Ekström, Tomas J

AU - Bakalkin, Georgy

AU - Schumann, Gunter

AU - IMAGEN Consortium

PY - 2019/2/1

Y1 - 2019/2/1

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 - SCORING: Journal article

C2 - 30525907

VL - 176

SP - 146

EP - 155

JO - AM J PSYCHIAT

JF - AM J PSYCHIAT

SN - 0002-953X

IS - 2

ER -