Genotype-dependent epigenetic regulation of DLGAP2 in alcohol use and dependence.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
10
04
2019
accepted:
30
10
2019
revised:
22
10
2019
pubmed:
21
11
2019
medline:
28
1
2022
entrez:
21
11
2019
Statut:
ppublish
Résumé
Alcohol misuse is a major public health problem originating from genetic and environmental risk factors. Alterations in the brain epigenome may orchestrate changes in gene expression that lead to alcohol misuse and dependence. Through epigenome-wide association analysis of DNA methylation from human brain tissues, we identified a differentially methylated region, DMR-DLGAP2, associated with alcohol dependence. Methylation within DMR-DLGAP2 was found to be genotype-dependent, allele-specific and associated with reward processing in brain. Methylation at the DMR-DLGAP2 regulated expression of DLGAP2 in vitro, and Dlgap2-deficient mice showed reduced alcohol consumption compared with wild-type controls. These results suggest that DLGAP2 may be an interface for genetic and epigenetic factors controlling alcohol use and dependence.
Identifiants
pubmed: 31745236
doi: 10.1038/s41380-019-0588-9
pii: 10.1038/s41380-019-0588-9
doi:
Substances chimiques
Dlgap2 protein, mouse
0
Nerve Tissue Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4367-4382Subventions
Organisme : Medical Research Council
ID : MR/N000390/1
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R00465X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S020306/1
Pays : United Kingdom
Organisme : NIBIB NIH HHS
ID : U54 EB020403
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG058854
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH085772
Pays : United States
Investigateurs
Tobias Banaschewski
(T)
Gareth J Barker
(GJ)
Arun L W Bokde
(ALW)
Erin Burke Quinlan
(EB)
Sylvane Desrivières
(S)
Herta Flor
(H)
Antoine Grigis
(A)
Hugh Garavan
(H)
Penny Gowland
(P)
Andreas Heinz
(A)
Bernd Ittermann
(B)
Jean-Luc Martinot
(JL)
Marie-Laure Paillère Martinot
(MP)
Eric Artiges
(E)
Frauke Nees
(F)
Dimitri Papadopoulos Orfanos
(DP)
Herve Lemaitre
(H)
Tomáš Paus
(T)
Luise Poustka
(L)
Sarah Hohmann
(S)
Sabina Millenet
(S)
Juliane H Fröhner
(JH)
Michael N Smolka
(MN)
Henrik Walter
(H)
Robert Whelan
(R)
Gunter Schumann
(G)
Informations de copyright
© 2019. The Author(s), under exclusive licence to Springer Nature Limited.
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