Alcohol Use Disorder-Associated DNA Methylation in the Nucleus Accumbens and Dorsolateral Prefrontal Cortex.

Autor:	White JD; GenOmics and Translational Research Center, RTI International, Research Triangle Park, North Carolina., Minto MS; GenOmics and Translational Research Center, RTI International, Research Triangle Park, North Carolina., Willis C; GenOmics and Translational Research Center, RTI International, Research Triangle Park, North Carolina., Quach BC; GenOmics and Translational Research Center, RTI International, Research Triangle Park, North Carolina., Han S; Lieber Institute for Brain Development, Baltimore, Maryland., Tao R; Lieber Institute for Brain Development, Baltimore, Maryland., Deep-Soboslay A; Lieber Institute for Brain Development, Baltimore, Maryland., Zillich L; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Witt SH; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Spanagel R; Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Hansson AC; Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Clark SL; Department of Psychiatry & Behavioral Sciences, Texas A&M University, College Station, Texas., van den Oord EJCG; Center for Biomarker Research and Precision Medicine, Virginia Commonwealth University, Richmond, Virgina., Hyde TM; Lieber Institute for Brain Development, Baltimore, Maryland., Mayfield RD; Waggoner Center for Alcohol and Addiction Research, the University of Texas at Austin, Austin, Texas., Webb BT; GenOmics and Translational Research Center, RTI International, Research Triangle Park, North Carolina., Johnson EO; GenOmics and Translational Research Center, RTI International, Research Triangle Park, North Carolina.; Fellow Program, RTI International, Research Triangle Park, North Carolina., Kleinman JE; Lieber Institute for Brain Development, Baltimore, Maryland., Bierut LJ; Department of Psychiatry, Washington University in Saint Louis School of Medicine, St. Louis, Missouri., Hancock DB; GenOmics and Translational Research Center, RTI International, Research Triangle Park, North Carolina.
Jazyk:	angličtina
Zdroj:	Biological psychiatry global open science [Biol Psychiatry Glob Open Sci] 2024 Aug 13; Vol. 4 (6), pp. 100375. Date of Electronic Publication: 2024 Aug 13 (Print Publication: 2024).
DOI:	10.1016/j.bpsgos.2024.100375
Abstrakt:	Background: Alcohol use disorder (AUD) has a profound public health impact. However, understanding of the molecular mechanisms that underlie the development and progression of AUD remains limited. Here, we investigated AUD-associated DNA methylation changes within and across 2 addiction-relevant brain regions, the nucleus accumbens and dorsolateral prefrontal cortex. Methods: Illumina HumanMethylation EPIC array data from 119 decedents (61 cases, 58 controls) were analyzed using robust linear regression with adjustment for technical and biological variables. Associations were characterized using integrative analyses of public annotation data and published genetic and epigenetic studies. We also tested for brain region-shared and brain region-specific associations using mixed-effects modeling and assessed implications of these results using public gene expression data from human brain. Results: At a false discovery rate of ≤.05, we identified 105 unique AUD-associated CpGs (annotated to 120 genes) within and across brain regions. AUD-associated CpGs were enriched in histone marks that tag active promoters, and our strongest signals were specific to a single brain region. Some concordance was found between our results and those of earlier published alcohol use or dependence methylation studies. Of the 120 genes, 23 overlapped with previous genetic associations for substance use behaviors, some of which also overlapped with previous addiction-related methylation studies. Conclusions: Our findings identify AUD-associated methylation signals and provide evidence of overlap with previous genetic and methylation studies. These signals may constitute predisposing genetic differences or robust methylation changes associated with AUD, although more work is needed to further disentangle the mechanisms that underlie these associations and their implications for AUD. (© 2024 The Authors.)
Databáze:	MEDLINE
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