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Multi-omics signatu...
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Zillich, LeaHeidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany.
(author)
Multi-omics signatures of alcohol use disorder in the dorsal and ventral striatum
- Article/chapterEnglish2022
Publisher, publication year, extent ...
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2022-05-06
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Springer Nature,2022
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-474870
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-474870URI
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https://doi.org/10.1038/s41398-022-01959-1DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Alcohol Use Disorder (AUD) is a major contributor to global mortality and morbidity. Postmortem human brain tissue enables the investigation of molecular mechanisms of AUD in the neurocircuitry of addiction. We aimed to identify differentially expressed (DE) genes in the ventral and dorsal striatum between individuals with AUD and controls, and to integrate the results with findings from genome- and epigenome-wide association studies (GWAS/EWAS) to identify functionally relevant molecular mechanisms of AUD. DNA-methylation and gene expression (RNA-seq) data was generated from postmortem brain samples of 48 individuals with AUD and 51 controls from the ventral striatum (VS) and the dorsal striatal regions caudate nucleus (CN) and putamen (PUT). We identified DE genes using DESeq2, performed gene-set enrichment analysis (GSEA), and tested enrichment of DE genes in results of GWASs using MAGMA. Weighted correlation network analysis (WGCNA) was performed for DNA-methylation and gene expression data and gene overlap was tested. Differential gene expression was observed in the dorsal (FDR < 0.05), but not the ventral striatum of AUD cases. In the VS, DE genes at FDR < 0.25 were overrepresented in a recent GWAS of problematic alcohol use. The ARHGEF15 gene was upregulated in all three brain regions. GSEA in CN and VS pointed towards cell-structure associated GO-terms and in PUT towards immune pathways. The WGCNA modules most strongly associated with AUD showed strong enrichment for immune response and inflammation pathways. Our integrated analysis of multi-omics data sets provides further evidence for the importance of immune- and inflammation-related processes in AUD.
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Poisel, EricHeidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany.
(author)
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Frank, JosefHeidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany.
(author)
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Foo, Jerome C.Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany.
(author)
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Friske, Marion M.Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Inst Psychopharmacol, Mannheim, Germany.
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Streit, FabianHeidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany.
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Sirignano, LeaHeidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany.
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Heilmann-Heimbach, StefanieUniv Bonn, Sch Med, Inst Human Genet, Bonn, Germany.;Univ Hosp Bonn, Bonn, Germany.
(author)
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Heimbach, AndreUniv Bonn, Sch Med, Inst Human Genet, Bonn, Germany.;Univ Hosp Bonn, Bonn, Germany.
(author)
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Hoffmann, PerUniv Bonn, Sch Med, Inst Human Genet, Bonn, Germany.;Univ Hosp Bonn, Bonn, Germany.;Univ Basel, Dept Biomed, CH-4003 Basel, Switzerland.
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Degenhardt, FranziskaUniv Duisburg Essen, Univ Hosp Essen, Dept Child & Adolescent Psychiat, Essen, Germany.
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Hansson, Anita C.Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Inst Psychopharmacol, Mannheim, Germany.
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Bakalkin, GeorgyUppsala universitet,Institutionen för farmaceutisk biovetenskap(Swepub:uu)gueba200
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Nothen, Markus M.Univ Bonn, Sch Med, Inst Human Genet, Bonn, Germany.;Univ Hosp Bonn, Bonn, Germany.
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Rietschel, MarcellaHeidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany.
(author)
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Spanagel, RainerHeidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Inst Psychopharmacol, Mannheim, Germany.
(author)
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Witt, Stephanie H.Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany.;Heidelberg Univ, Med Fac Mannheim, Ctr Innovat Psychiat & Psychotherapeut Res, Cent Inst Mental Hlth,Biobank, Mannheim, Germany.
(author)
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Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany.Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Inst Psychopharmacol, Mannheim, Germany.
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In:Translational Psychiatry: Springer Nature12:12158-3188
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Zillich, Lea
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Poisel, Eric
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Frank, Josef
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Sirignano, Lea
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