Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
QIMR Home Page
GenEpi Home Page
About GenEpi
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet
PMID
41619726
TITLE
Runx1 transcription factor modulates opioid analgesia and withdrawal in humans and rodents.
ABSTRACT
Opioid analgesia and adverse outcomes vary across individuals. We show that runt-related transcription factor 1 (Runx1) modulates the microglial transcriptome and is a genetic determinant of opioid antinociceptive responses and withdrawal. In mice, Runx1 deletion in microglia produces distinct ultrastructural and transcriptomic signatures, reducing morphine potency despite no prior opioid exposure. These mice also require greater post-operative morphine and display exacerbated morphine-induced hyperalgesia and withdrawal. Single-cell RNA sequencing (scRNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) analyses reveal a unique microglial state, with Runx1 regulating inflammatory signaling and key microglial functions. In humans, association analyses link RUNX1 variants to inter-individual differences in perioperative opioid requirement and withdrawal severity. Identifying RUNX1 susceptibility genotypes may be important for understanding individual variability in opioid responses, with potential relevance for future personalized approaches.
Copyright © 2025 Elsevier Inc. All rights reserved.
DATE PUBLISHED
2026 Jan 30
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2025/04/03
revised 2025/10/08
accepted 2025/11/17
medline 2026/02/01 00:44
pubmed 2026/02/01 00:44
entrez 2026/01/31 18:40
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Leduc-Pessah H Leduc-Pessah Heather H Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada.
McAllister BB McAllister Brendan B BB Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada.
Sinha S Sinha Sarthak S Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
Stokes-Heck S Stokes-Heck Sierra S Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada.
Nishizawa D Nishizawa Daisuke D Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan; Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
Fan CY Fan Churmy Y CY Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada.
St-Pierre MK St-Pierre Marie-Kim MK School of Medical Sciences, University of Victoria, Victoria, BC, Canada.
Bradaia A Bradaia Amyaouch A Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB T2N 4N1, Canada.
Defaye M Defaye Manon M Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB T2N 4N1, Canada.
Burma NE Burma Nicole E NE Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada.
Damblon J Damblon Jonathan J CERVO Brain Research Centre, Québec Mental Health Institute, Graduate program in Neuroscience, Université Laval University, Department of Psychiatry and Neuroscience, Department of Anesthesiology & Intensive Care, Université Laval, Quebec City, QC, Canada.
Muñoz-Pino E Muñoz-Pino Einer E CERVO Brain Research Centre, Québec Mental Health Institute, Graduate program in Neuroscience, Université Laval University, Department of Psychiatry and Neuroscience, Department of Anesthesiology & Intensive Care, Université Laval, Quebec City, QC, Canada.
Visser F Visser Frank F Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada.
Dorion MF Dorion Marie-France MF Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
Healy LM Healy Luke M LM Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
Tang YM Tang Ye Man YM Department of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill University, Montreal, QC, Canada.
Canet-Pons J Canet-Pons Julia J Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada.
van den Hoogen NJ van den Hoogen Nynke J NJ Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada.
Zhang Z Zhang Zizhen Z Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Clinical Neurosciences, University of Calgary, Calgary, AB, T2N RN1, Canada.
Antunes FTT Antunes Flavia T T FTT Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Clinical Neurosciences, University of Calgary, Calgary, AB, T2N RN1, Canada.
Piscopo VEC Piscopo Valerio E C VEC Department of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill University, Montreal, QC, Canada.
Medina M Medina Margaret M Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada.
Fukuda KI Fukuda Ken-Ichi KI Department of Oral Health and Clinical Science, Tokyo Dental College, 2-9-18, Misaki-cho, Chiyoda-ku, Tokyo 101-0061, Japan.
Ichinohe T Ichinohe Tatsuya T Department of Dental Anesthesiology, Tokyo Dental College, 2-9-18, Misaki-cho, Chiyoda-ku, Tokyo 101-0061, Japan.
Nagashima M Nagashima Makoto M Department of Surgery, Toho University Sakura Medical Center, 564-1, Shimoshizu, Sakura-shi, Chiba 285-8741, Japan.
Hayashida M Hayashida Masakazu M Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan; Department of Anesthesiology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka, Saitama 350-1298, Japan; Department of Anesthesiology and Pain Medicine, Juntendo University School of Medicine, 2-1-1, Hongou, Bunkyou-ku, Tokyo 113-8421, Japan.
Johnson E Johnson Emma E Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Agrawal A Agrawal Arpana A Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Degenhardt L Degenhardt Louisa L National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW, Australia.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Zamponi GW Zamponi Gerald W GW Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Clinical Neurosciences, University of Calgary, Calgary, AB, T2N RN1, Canada.
Nelson EC Nelson Elliot C EC Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Altier C Altier Christophe C Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB T2N 4N1, Canada.
Tremblay ME Tremblay Marie-Eve ME School of Medical Sciences, University of Victoria, Victoria, BC, Canada.
Bousman C Bousman Chad C Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Medical Genetics, and Department of Psychiatry, University of Calgary, Calgary, AB, Canada.
Stifani S Stifani Stefano S Department of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill University, Montreal, QC, Canada.
De Koninck Y De Koninck Yves Y CERVO Brain Research Centre, Québec Mental Health Institute, Graduate program in Neuroscience, Université Laval University, Department of Psychiatry and Neuroscience, Department of Anesthesiology & Intensive Care, Université Laval, Quebec City, QC, Canada.
Ikeda K Ikeda Kazutaka K Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan; Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
Biernaskie J Biernaskie Jeff J Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Surgery, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
Trang T Trang Tuan T Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada. Electronic address: trangt@ucalgary.ca.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Neuron
ISOABBREVIATION: Neuron
YEAR: 2026
MONTH: Jan
DAY: 30
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1097-4199
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Neuron
COUNTRY: United States
ISSNLINKING: 0896-6273
NLMUNIQUEID: 8809320
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
GENERAL NOTE
KEYWORDS
KEYWORD
genetics
microglia
opioid analgesia
opioid withdrawal
personalized medicine
transcription factor
transcriptomics
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
Designed by: GenEpi IT
Maintained by: GenEpi IT
Feedback: webmaster
Copyright © 2007 QIMR
For more information Contact Us
epiit@qimr.edu.au
Last Modified: Oct 15 2007