Epigenome-wide association study and multi-tissue replication of individuals with alcohol use disorder: evidence for abnormal glucocorticoid signaling pathway gene regulation.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
05
11
2019
accepted:
14
04
2020
revised:
13
03
2020
pubmed:
14
5
2020
medline:
12
10
2021
entrez:
14
5
2020
Statut:
ppublish
Résumé
Alcohol use disorder (AUD) is a chronic debilitating disorder with limited treatment options and poorly defined pathophysiology. There are substantial genetic and epigenetic components; however, the underlying mechanisms contributing to AUD remain largely unknown. We conducted the largest DNA methylation epigenome-wide association study (EWAS) analyses currently available for AUD (total N = 625) and employed a top hit replication (N = 4798) using a cross-tissue/cross-phenotypic approach with the goal of identifying novel epigenetic targets relevant to AUD. Results show that a network of differentially methylated regions in glucocorticoid signaling and inflammation-related genes were associated with alcohol use behaviors. A top probe consistently associated across all cohorts was located in the long non-coding RNA growth arrest specific five gene (GAS5) (p < 10
Identifiants
pubmed: 32398718
doi: 10.1038/s41380-020-0734-4
pii: 10.1038/s41380-020-0734-4
pmc: PMC7658001
mid: NIHMS1584992
doi:
Substances chimiques
Glucocorticoids
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2224-2237Subventions
Organisme : Intramural NIH HHS
ID : Z99 AA999999
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_19009
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 104036/Z/14/Z
Pays : United Kingdom
Organisme : Chief Scientist Office
ID : CZD/16/6
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_15018
Pays : United Kingdom
Organisme : NIAAA NIH HHS
ID : R28 AA012725
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : G9815508
Pays : United Kingdom
Organisme : Intramural NIH HHS
ID : ZIA AA000242
Pays : United States
Informations de copyright
© 2020. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
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