@article{c2f77addba1e4f219816a712cd36f19b,
title = "Dual methylation and hydroxymethylation study of alcohol use disorder",
abstract = "Using an integrative, multi-tissue design, we sought to characterize methylation and hydroxymethylation changes in blood and brain associated with alcohol use disorder (AUD). First, we used epigenomic deconvolution to perform cell-type-specific methylome-wide association studies within subpopulations of granulocytes/T-cells/B-cells/monocytes in 1132 blood samples. Blood findings were then examined for overlap with AUD-related associations with methylation and hydroxymethylation in 50 human post-mortem brain samples. Follow-up analyses investigated if overlapping findings mediated AUD-associated transcription changes in the same brain samples. Lastly, we replicated our blood findings in an independent sample of 412 individuals and aimed to replicate published alcohol methylation findings using our results. Cell-type-specific analyses in blood identified methylome-wide significant associations in monocytes and T-cells. The monocyte findings were significantly enriched for AUD-related methylation and hydroxymethylation in brain. Hydroxymethylation in specific sites mediated AUD-associated transcription in the same brain samples. As part of the most comprehensive methylation study of AUD to date, this work involved the first cell-type-specific methylation study of AUD conducted in blood, identifying and replicating a finding in DLGAP1 that may be a blood-based biomarker of AUD. In this first study to consider the role of hydroxymethylation in AUD, we found evidence for a novel mechanism for cognitive deficits associated with AUD. Our results suggest promising new avenues for AUD research.",
keywords = "alcohol use disorder, hydroxymethylation, methylation",
author = "Clark, {Shaunna L.} and Chan, {Robin F.} and Min Zhao and Xie, {Lin Y.} and Copeland, {William E.} and Penninx, {Brenda W. J. H.} and Aberg, {Karolina A.} and {van den Oord}, {Edwin J. C. G.}",
note = "Funding Information: Tissues were received from the New South Wales Brain Tissue Resource Centre at the University of Sydney. Research reported in this publication was supported by the National Institute of Alcohol Abuse and Alcoholism of the National Institutes of Health under Award Number R28AA012725. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health. Funding Information: This study was supported by the National Institutes of Health (R01MH099110 and 1R01MH104576 to E.J.C.G. and 1R01AA026057 to S.L.C.), the VCU CTSA (UL1TR002649) from the National Institutes of Health's National Center for Advancing Translation Science and CCTR Endowment Fund of the Virginia Commonwealth University, and a NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation. The funding sources had no role in the study design, writing of the report or decision to submit the article for publication. The infrastructure for the NESDA study (www.nesda.nl) is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development (ZonMw, grant number 10-000-1002) and financial contributions by participating universities and mental health care organizations (VU University Medical Center, GGZ inGeest, Leiden University Medical Center, Leiden University, GGZ Rivierduinen, University Medical Center Groningen, University of Groningen, Lentis, GGZ Friesland, GGZ Drenthe, Rob Giel Onderzoekscentrum). Tissues were received from the New South Wales Brain Tissue Resource Centre at the University of Sydney. Research reported in this publication was supported by the National Institute of Alcohol Abuse and Alcoholism of the National Institutes of Health under Award Number R28AA012725. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health. Funding Information: This study was supported by the National Institutes of Health (R01MH099110 and 1R01MH104576 to E.J.C.G. and 1R01AA026057 to S.L.C.), the VCU CTSA (UL1TR002649) from the National Institutes of Health's National Center for Advancing Translation Science and CCTR Endowment Fund of the Virginia Commonwealth University, and a NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation. The funding sources had no role in the study design, writing of the report or decision to submit the article for publication. Funding Information: The infrastructure for the NESDA study ( www.nesda.nl ) is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development (ZonMw, grant number 10‐000‐1002) and financial contributions by participating universities and mental health care organizations (VU University Medical Center, GGZ inGeest, Leiden University Medical Center, Leiden University, GGZ Rivierduinen, University Medical Center Groningen, University of Groningen, Lentis, GGZ Friesland, GGZ Drenthe, Rob Giel Onderzoekscentrum). Publisher Copyright: {\textcopyright} 2021 Society for the Study of Addiction.",
year = "2022",
month = mar,
doi = "https://doi.org/10.1111/adb.13114",
language = "English",
volume = "27",
journal = "Addiction biology",
issn = "1355-6215",
publisher = "Wiley-Blackwell",
number = "2",
}