An emerging multi-omic understanding of the genetics of opioid addiction

Johnson, Eric O.; Fisher, Heidi S.; Sullivan, Kyle A.; Corradin, Olivia; Sanchez-Roige, Sandra; Gaddis, Nathan C.; Sami, Yasmine N.; Townsend, Alice; Prates, Erica Teixeira; Pavicic, Mirko Venegas; Kruse, Peter; Chesler, Elissa J.; Palmer, Abraham A.; Troiani, Vanessa; Bubier, Jason A.; Jacobson, Daniel A.; Maher, Brion S.

doi:10.1172/jci172886

An emerging multi-omic understanding of the genetics of opioid addiction

Journal Article · Tue Oct 15 00:00:00 EDT 2024 · Journal of Clinical Investigation

DOI:https://doi.org/10.1172/jci172886· OSTI ID:2474759

Johnson, Eric O. ^[1]; Fisher, Heidi S. ^[2]; ^[3]; Corradin, Olivia ^[4]; Sanchez-Roige, Sandra ^[5]; Gaddis, Nathan C. ^[1]; Sami, Yasmine N. ^[4]; Townsend, Alice ^[3]; ^[3]; ^[3]; Kruse, Peter ^[3]; Chesler, Elissa J. ^[2]; ^[6]; Troiani, Vanessa ^[7]; Bubier, Jason A. ^[2]; ^[3]; Maher, Brion S. ^[8]

RTI International, Research Triangle Park, NC (United States)
The Jackson Laboratory, Bar Harbor, ME (United States)
Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
Massachusetts Institute of Technology (MIT), Cambridge, MA (United States)
University of California San Diego, La Jolla, CA (United States); Vanderbilt University Medical Center, Nashville, TN (United States)
University of California San Diego, La Jolla, CA (United States)
Geisinger College of Health Sciences, Scranton, PA (United States)
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (United States)

Opioid misuse, addiction, and associated overdose deaths remain global public health crises. Despite the tremendous need for pharmacological treatments, current options are limited in number, use, and effectiveness. Fundamental leaps forward in our understanding of the biology driving opioid addiction are needed to guide development of more effective medication-assisted therapies. This Review focuses on the omics-identified biological features associated with opioid addiction. Recent GWAS have begun to identify robust genetic associations, including variants in OPRM1, FURIN, and the gene cluster SCAI/PPP6C/RABEPK. An increasing number of omics studies of postmortem human brain tissue examining biological features (e.g., histone modification and gene expression) across different brain regions have identified broad gene dysregulation associated with overdose death among opioid misusers. Drawn together by meta-analysis and multi-omic systems biology, and informed by model organism studies, key biological pathways enriched for opioid addiction–associated genes are emerging, which include specific receptors (e.g., GABAB receptors, GPCR, and Trk) linked to signaling pathways (e.g., Trk, ERK/MAPK, orexin) that are associated with synaptic plasticity and neuronal signaling. Studies leveraging the agnostic discovery power of omics and placing it within the context of functional neurobiology will propel us toward much-needed, field-changing breakthroughs, including identification of actionable targets for drug development to treat this devastating brain disease.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 2474759

Journal Information:: Journal of Clinical Investigation, Journal Name: Journal of Clinical Investigation Journal Issue: 20 Vol. 134; ISSN 1558-8238

Publisher:: American Society for Clinical InvestigationCopyright Statement

Country of Publication:: United States

Language:: English

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