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Profiling neuronal methylome and hydroxymethylome of opioid use disorder in the human orbitofrontal cortex

Author

Listed:
  • Gregory Rompala

    (Icahn School of Medicine at Mount Sinai)

  • Sheila T. Nagamatsu

    (Yale University School of Medicine
    VA Connecticut Healthcare System
    Clinical Neurosciences Division)

  • José Jaime Martínez-Magaña

    (Yale University School of Medicine
    VA Connecticut Healthcare System
    Clinical Neurosciences Division)

  • Diana L. Nuñez-Ríos

    (Yale University School of Medicine
    VA Connecticut Healthcare System
    Clinical Neurosciences Division)

  • Jiawei Wang

    (Yale University
    Yale School of Public Health)

  • Matthew J. Girgenti

    (Yale University School of Medicine
    Clinical Neurosciences Division)

  • John H. Krystal

    (Yale University School of Medicine
    VA Connecticut Healthcare System
    Clinical Neurosciences Division)

  • Joel Gelernter

    (Yale University School of Medicine
    VA Connecticut Healthcare System
    Clinical Neurosciences Division)

  • Yasmin L. Hurd

    (Icahn School of Medicine at Mount Sinai)

  • Janitza L. Montalvo-Ortiz

    (Yale University School of Medicine
    VA Connecticut Healthcare System
    Clinical Neurosciences Division)

Abstract

Opioid 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.

Suggested Citation

  • Gregory Rompala & Sheila T. Nagamatsu & José Jaime Martínez-Magaña & Diana L. Nuñez-Ríos & Jiawei Wang & Matthew J. Girgenti & John H. Krystal & Joel Gelernter & Yasmin L. Hurd & Janitza L. Montalvo-O, 2023. "Profiling neuronal methylome and hydroxymethylome of opioid use disorder in the human orbitofrontal cortex," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40285-y
    DOI: 10.1038/s41467-023-40285-y
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    References listed on IDEAS

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    1. Kyoko Watanabe & Erdogan Taskesen & Arjen Bochoven & Danielle Posthuma, 2017. "Functional mapping and annotation of genetic associations with FUMA," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    2. Swathi V. Iyer & Atul Ranjan & Harold K. Elias & Alejandro Parrales & Hiromi Sasaki & Badal C. Roy & Shahid Umar & Ossama W. Tawfik & Tomoo Iwakuma, 2016. "Genome-wide RNAi screening identifies TMIGD3 isoform1 as a suppressor of NF-κB and osteosarcoma progression," Nature Communications, Nature, vol. 7(1), pages 1-13, December.
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    1. BaDoi N. Phan & Madelyn H. Ray & Xiangning Xue & Chen Fu & Robert J. Fenster & Stephen J. Kohut & Jack Bergman & Suzanne N. Haber & Kenneth M. McCullough & Madeline K. Fish & Jill R. Glausier & Qiao S, 2024. "Single nuclei transcriptomics in human and non-human primate striatum in opioid use disorder," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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