{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T14:02:29Z","timestamp":1782309749136,"version":"3.54.5"},"reference-count":67,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T00:00:00Z","timestamp":1739491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Research Foundation (Deutsche Forschungsgemeinschaft, DFG)","award":["DFG NI 1332\/13-1"],"award-info":[{"award-number":["DFG NI 1332\/13-1"]}]},{"name":"German Research Foundation (Deutsche Forschungsgemeinschaft, DFG)","award":["01EE2306B"],"award-info":[{"award-number":["01EE2306B"]}]},{"name":"Federal Ministry of Education and Research (Bundesministerium f\u00fcr Bildung und Forschung [BMBF])","award":["DFG NI 1332\/13-1"],"award-info":[{"award-number":["DFG NI 1332\/13-1"]}]},{"name":"Federal Ministry of Education and Research (Bundesministerium f\u00fcr Bildung und Forschung [BMBF])","award":["01EE2306B"],"award-info":[{"award-number":["01EE2306B"]}]},{"name":"ministry of Baden-W\u00fcrttemberg within the initial phase of the German Center for Mental Health (DZPG)","award":["DFG NI 1332\/13-1"],"award-info":[{"award-number":["DFG NI 1332\/13-1"]}]},{"name":"ministry of Baden-W\u00fcrttemberg within the initial phase of the German Center for Mental Health (DZPG)","award":["01EE2306B"],"award-info":[{"award-number":["01EE2306B"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alcohol use disorder (AUD) contributes significantly to the global burden of disease. The susceptibility for AUD is mediated through an interaction of genetic risk factors and environmental influences. These gene \u00d7 environment (G \u00d7 E) interactions manifest as epigenetic regulations of gene expression, among other things. Previous research suggests an association between Ganglioside Induced Differentiation Associated Protein 1 (GDAP1) DNA methylation and AUD. Here, we investigate the epigenetic dysregulation of GDAP1 in AUD through comparing DNA methylation in whole blood and saliva, as well as H3K4-trimethylation (H3K4me3) in PBMC (Peripheral Blood Mononuclear Cell) samples of AUD patients and healthy control individuals. Additionally, the effect of abstinence-based therapy was investigated. AUD patients before treatment exhibit significantly lower promoter DNA methylation levels in whole blood and saliva, as well as lower H3K4me3 near the transcription start site. GDAP1 gene expression was not significantly altered. Following treatment, H3K4me3 was significantly increased in patients and no longer differed from control individuals. There was no significant effect of treatment on DNA methylation. We conclude that GDAP1 is epigenetically dysregulated in AUD patients, and is responsive to abstinence-based therapy at the level of H3K4me3. It should be investigated further to establish its potential as a diagnostic biomarker.<\/jats:p>","DOI":"10.3390\/ijms26041623","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T03:20:52Z","timestamp":1739503252000},"page":"1623","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["GDAP1 Is Dysregulated at DNA Methylation and H3K4me3 Levels in Alcohol Use Disorder"],"prefix":"10.3390","volume":"26","author":[{"given":"Emilia","family":"Kawecka","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Hospital of Tuebingen, Eberhard Karls University of Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Pl\u00e4ttner","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Hospital of Tuebingen, Eberhard Karls University of Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Ederer","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Hospital of Tuebingen, Eberhard Karls University of Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kilian","family":"Niemann","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Hospital of Tuebingen, Eberhard Karls University of Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Pasche","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Hospital of Tuebingen, Eberhard Karls University of Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milan","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Hospital of Tuebingen, Eberhard Karls University of Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Edelmann","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Hospital of Tuebingen, Eberhard Karls University of Tuebingen, 72076 Tuebingen, Germany"},{"name":"German Center for Mental Health (DZPG), Partner Site Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7884-4500","authenticated-orcid":false,"given":"Vanessa","family":"Nieratschker","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Hospital of Tuebingen, Eberhard Karls University of Tuebingen, 72076 Tuebingen, Germany"},{"name":"German Center for Mental Health (DZPG), Partner Site Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1016\/S0140-6736(12)61766-8","article-title":"A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990\u20132010: A systematic analysis for the Global Burden of Disease Study 2010","volume":"380","author":"Lim","year":"2012","journal-title":"Lancet"},{"key":"ref_2","unstructured":"Vladimir Poznyak, D.R. 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