Exploring opportunities for drug repurposing and precision medicine in cannabis use disorder using genetics. 2023

Laura A Greco, and William R Reay, and Christopher V Dayas, and Murray J Cairns
School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, New South Wales, Australia.

Cannabis use disorder (CUD) remains a significant public health issue globally, affecting up to one in five adults who use cannabis. Despite extensive research into the molecular underpinnings of the condition, there are no effective pharmacological treatment options available. Therefore, we sought to further explore genetic analyses to prioritise opportunities to repurpose existing drugs for CUD. Specifically, we aimed to identify druggable genes associated with the disorder, integrate transcriptomic/proteomic data and estimate genetic relationships with clinically actionable biochemical traits. Aggregating variants to genes based on genomic position, prioritised the phosphodiesterase gene PDE4B as an interesting target for drug repurposing in CUD. Credible causal PDE4B variants revealed by probabilistic finemapping in and around this locus demonstrated an association with inflammatory and other substance use phenotypes. Gene and protein expression data integrated with the GWAS data revealed a novel CUD associated gene, NPTX1, in whole blood and supported a role for hyaluronidase, a key enzyme in the extracellular matrix in the brain and other tissues. Finally, genetic correlation with biochemical traits revealed a genetic overlap between CUD and immune-related markers such as lymphocyte count, as well as serum triglycerides.

UI MeSH Term Description Entries
D002188 Cannabis The plant genus in the Cannabaceae plant family, Urticales order, Hamamelidae subclass. The flowering tops are called many slang terms including pot, marijuana, hashish, bhang, and ganja. The stem is an important source of hemp fiber. Bhang,Ganja,Hashish,Hemp,Cannabis indica,Cannabis sativa,Hemp Plant,Marihuana,Marijuana,Bhangs,Cannabi,Ganjas,Hashishs,Hemp Plants,Hemps,Plant, Hemp,Plants, Hemp
D002189 Marijuana Abuse Use of marijuana associated with abnormal psychological, social, and or occupational functioning. Cannabis Abuse,Cannabis Dependence,Cannabis-Related Disorder,Hashish Abuse,Marijuana Dependence,Marihuana Abuse,Abuse, Cannabis,Abuse, Hashish,Abuse, Marihuana,Abuse, Marijuana,Cannabis Related Disorder,Dependence, Cannabis,Dependence, Marijuana,Disorder, Cannabis-Related
D057285 Precision Medicine Clinical, therapeutic and diagnostic approaches to optimal disease management based on individual variations in a patient's genetic profile. Individualized Medicine,Predictive Medicine,P Health,P-Health,Personalized Medicine,Theranostics,Medicine, Individualized,Medicine, Personalized,Medicine, Precision,Medicine, Predictive,Theranostic
D058492 Drug Repositioning The deliberate and methodical practice of finding new applications for existing drugs. Drug Repurposing,Drug Rescue,Repositioning, Drug,Repurposing, Drug,Rescue, Drug
D019966 Substance-Related Disorders Disorders related to substance use or abuse. Chemical Dependence,Drug Abuse,Drug Addiction,Drug Dependence,Drug Habituation,Drug Use Disorder,Drug Use Disorders,Organic Mental Disorders, Substance-Induced,Substance Abuse,Substance Dependence,Substance Related Disorder,Substance Use,Substance Use Disorder,Substance Use Disorders,Prescription Drug Abuse,Substance Addiction,Abuse, Drug,Abuse, Prescription Drug,Abuse, Substance,Addiction, Drug,Addiction, Substance,Chemical Dependences,Dependence, Chemical,Dependence, Drug,Dependence, Substance,Dependences, Chemical,Disorder, Drug Use,Disorder, Substance Related,Disorder, Substance Use,Disorders, Substance Related,Drug Abuse, Prescription,Habituation, Drug,Organic Mental Disorders, Substance Induced,Related Disorder, Substance,Related Disorders, Substance,Substance Abuses,Substance Uses,Use, Substance
D040901 Proteomics The systematic study of the complete complement of proteins (PROTEOME) of organisms. Peptidomics

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