Profiling neuronal methylome and hydroxymethylome of opioid use disorder in the human orbitofrontal cortex
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Published:2023-07-28
Issue:1
Volume:14
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Rompala Gregory, Nagamatsu Sheila T.ORCID, Martínez-Magaña José JaimeORCID, Nuñez-Ríos Diana L., Wang JiaweiORCID, Girgenti Matthew J.ORCID, Krystal John H.ORCID, Gelernter JoelORCID, Alvarez Victor E., Benedek David, Che Alicia, Cruz Dianne A., Davis David A., Girgenti Matthew J., Hoffman Ellen, Holtzheimer Paul E., Huber Bertrand R., Kaye Alfred, Krystal John H., Labadorf Adam T., Keane Terence M., Logue Mark W., McKee Ann, Marx Brian, Miller Mark W., Noller Crystal, Montalvo-Ortiz Janitza, Scott William K., Schnurr Paula, Stein Thor, Ursano Robert, Williamson Douglas E., Wolf Erika J., Young Keith A., Hurd Yasmin L.ORCID, Montalvo-Ortiz Janitza L.ORCID,
Abstract
AbstractOpioid use disorder (OUD) is influenced by genetic and environmental factors. While recent research suggests epigenetic disturbances in OUD, this is mostly limited to DNA methylation (5mC). DNA hydroxymethylation (5hmC) has been widely understudied. We conducted a multi-omics profiling of OUD in a male cohort, integrating neuronal-specific 5mC and 5hmC as well as gene expression profiles from human postmortem orbitofrontal cortex (OUD = 12; non-OUD = 26). Single locus methylomic analysis and co-methylation analysis showed a higher number of OUD-associated genes and gene networks for 5hmC compared to 5mC; these were enriched for GPCR, Wnt, neurogenesis, and opioid signaling. 5hmC marks also showed a higher correlation with gene expression patterns and enriched for GWAS of psychiatric traits. Drug interaction analysis revealed interactions with opioid-related drugs, some used as OUD treatments. Our multi-omics findings suggest an important role of 5hmC and reveal loci epigenetically dysregulated in OFC neurons of individuals with OUD.
Funder
U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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