IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-40285-y.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-40285-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-40285-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. 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.
    2. 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.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    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.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Natalie DeForest & Yuqi Wang & Zhiyi Zhu & Jacqueline S. Dron & Ryan Koesterer & Pradeep Natarajan & Jason Flannick & Tiffany Amariuta & Gina M. Peloso & Amit R. Majithia, 2024. "Genome-wide discovery and integrative genomic characterization of insulin resistance loci using serum triglycerides to HDL-cholesterol ratio as a proxy," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Shahram Bahrami & Kaja Nordengen & Jaroslav Rokicki & Alexey A. Shadrin & Zillur Rahman & Olav B. Smeland & Piotr P. Jaholkowski & Nadine Parker & Pravesh Parekh & Kevin S. O’Connell & Torbjørn Elvsås, 2024. "The genetic landscape of basal ganglia and implications for common brain disorders," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    3. Bhuwan Khatri & Kandice L. Tessneer & Astrid Rasmussen & Farhang Aghakhanian & Tove Ragna Reksten & Adam Adler & Ilias Alevizos & Juan-Manuel Anaya & Lara A. Aqrawi & Eva Baecklund & Johan G. Brun & S, 2022. "Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Mathias Seviiri & Matthew H. Law & Jue-Sheng Ong & Puya Gharahkhani & Pierre Fontanillas & Catherine M. Olsen & David C. Whiteman & Stuart MacGregor, 2022. "A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    5. Paul R. H. J. Timmers & James F. Wilson & Peter K. Joshi & Joris Deelen, 2020. "Multivariate genomic scan implicates novel loci and haem metabolism in human ageing," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    6. Zhen Qiao & Julia Sidorenko & Joana A. Revez & Angli Xue & Xueling Lu & Katri Pärna & Harold Snieder & Peter M. Visscher & Naomi R. Wray & Loic Yengo, 2023. "Estimation and implications of the genetic architecture of fasting and non-fasting blood glucose," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    7. Danni A. Gadd & Robert F. Hillary & Daniel L. McCartney & Liu Shi & Aleks Stolicyn & Neil A. Robertson & Rosie M. Walker & Robert I. McGeachan & Archie Campbell & Shen Xueyi & Miruna C. Barbu & Claire, 2022. "Integrated methylome and phenome study of the circulating proteome reveals markers pertinent to brain health," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    8. Fasil Tekola-Ayele & Xuehuo Zeng & Suvo Chatterjee & Marion Ouidir & Corina Lesseur & Ke Hao & Jia Chen & Markos Tesfaye & Carmen J. Marsit & Tsegaselassie Workalemahu & Ronald Wapner, 2022. "Placental multi-omics integration identifies candidate functional genes for birthweight," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    9. Xingjie Hao & Zhonghe Shao & Ning Zhang & Minghui Jiang & Xi Cao & Si Li & Yunlong Guan & Chaolong Wang, 2023. "Integrative genome-wide analyses identify novel loci associated with kidney stones and provide insights into its genetic architecture," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    10. Wendiao Zhang & Ming Zhang & Zhenhong Xu & Hongye Yan & Huimin Wang & Jiamei Jiang & Juan Wan & Beisha Tang & Chunyu Liu & Chao Chen & Qingtuan Meng, 2023. "Human forebrain organoid-based multi-omics analyses of PCCB as a schizophrenia associated gene linked to GABAergic pathways," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    11. Bingxin Zhao & Yujue Li & Zirui Fan & Zhenyi Wu & Juan Shu & Xiaochen Yang & Yilin Yang & Xifeng Wang & Bingxuan Li & Xiyao Wang & Carlos Copana & Yue Yang & Jinjie Lin & Yun Li & Jason L. Stein & Joa, 2024. "Eye-brain connections revealed by multimodal retinal and brain imaging genetics," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    12. Isabelle Austin-Zimmerman & Daniel F. Levey & Olga Giannakopoulou & Joseph D. Deak & Marco Galimberti & Keyrun Adhikari & Hang Zhou & Spiros Denaxas & Haritz Irizar & Karoline Kuchenbaecker & Andrew M, 2023. "Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    13. Devansh Pandey & Mariana Harris & Nandita R. Garud & Vagheesh M. Narasimhan, 2024. "Leveraging ancient DNA to uncover signals of natural selection in Europe lost due to admixture or drift," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    14. Peter Zhukovsky & Earvin S. Tio & Gillian Coughlan & David A. Bennett & Yanling Wang & Timothy J. Hohman & Diego A. Pizzagalli & Benoit H. Mulsant & Aristotle N. Voineskos & Daniel Felsky, 2024. "Genetic influences on brain and cognitive health and their interactions with cardiovascular conditions and depression," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    15. Yuki Ishikawa & Nao Tanaka & Yoshihide Asano & Masanari Kodera & Yuichiro Shirai & Mitsuteru Akahoshi & Minoru Hasegawa & Takashi Matsushita & Kazuyoshi Saito & Sei-ichiro Motegi & Hajime Yoshifuji & , 2024. "GWAS for systemic sclerosis identifies six novel susceptibility loci including one in the Fcγ receptor region," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    16. Jie Huang & Jennifer E. Huffman & Yunfeng Huang & Ítalo Valle & Themistocles L. Assimes & Sridharan Raghavan & Benjamin F. Voight & Chang Liu & Albert-László Barabási & Rose D. L. Huang & Qin Hui & Xu, 2022. "Genomics and phenomics of body mass index reveals a complex disease network," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    17. Eva-Maria Stauffer & Richard A. I. Bethlehem & Lena Dorfschmidt & Hyejung Won & Varun Warrier & Edward T. Bullmore, 2023. "The genetic relationships between brain structure and schizophrenia," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    18. Amirthagowri Ambalavanan & Le Chang & Jihoon Choi & Yang Zhang & Sara A. Stickley & Zhi Y. Fang & Kozeta Miliku & Bianca Robertson & Chloe Yonemitsu & Stuart E. Turvey & Piushkumar J. Mandhane & Elino, 2024. "Human milk oligosaccharides are associated with maternal genetics and respiratory health of human milk-fed children," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    19. Roy Oelen & Dylan H. Vries & Harm Brugge & M. Grace Gordon & Martijn Vochteloo & Chun J. Ye & Harm-Jan Westra & Lude Franke & Monique G. P. Wijst, 2022. "Single-cell RNA-sequencing of peripheral blood mononuclear cells reveals widespread, context-specific gene expression regulation upon pathogenic exposure," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    20. Keira J A Johnston & Joey Ward & Pradipta R Ray & Mark J Adams & Andrew M McIntosh & Blair H Smith & Rona J Strawbridge & Theodore J Price & Daniel J Smith & Barbara I Nicholl & Mark E S Bailey, 2021. "Sex-stratified genome-wide association study of multisite chronic pain in UK Biobank," PLOS Genetics, Public Library of Science, vol. 17(4), pages 1-27, April.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40285-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.