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Genotype-dependent epigenetic regulation of DLGAP2 in alcohol use and dependence.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.ORCID iD: 0000-0002-1332-7067
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2019 (English)In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578Article in journal (Refereed) Epub ahead of print
Abstract [en]

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.

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2019.
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-399982DOI: 10.1038/s41380-019-0588-9PubMedID: 31745236OAI: oai:DiVA.org:uu-399982DiVA, id: diva2:1379693
Available from: 2019-12-17 Created: 2019-12-17 Last updated: 2020-02-17Bibliographically approved

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Kononenko, OlgaSarkisyan, DaniilWatanabe, HiroyukiBakalkin, Georgy

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