- Title
- Exploring opportunities for drug repurposing and precision medicine in cannabis use disorder using genetics
- Creator
- Greco, Laura A.; Reay, William R.; Dayas, Christopher V.; Cairns, Murray J.
- Relation
- NHMRC.1121474 http://purl.org/au-research/grants/nhmrc/1121474
- Relation
- Addiction Biology Vol. 28, Issue 8, no. e13313
- Publisher Link
- http://dx.doi.org/10.1111/adb.13313
- Publisher
- Wiley-Blackwell
- Resource Type
- journal article
- Date
- 2023
- Description
- 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.
- Subject
- cannabis use disorder; genetics; pharmacotherapy
- Identifier
- http://hdl.handle.net/1959.13/1485817
- Identifier
- uon:51705
- Identifier
- ISSN:1355-6215
- Rights
- © 2023 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction. This is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Language
- eng
- Full Text
- Reviewed
- Hits: 571
- Visitors: 625
- Downloads: 59
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT02 | Publisher version (open access) | 1 MB | Adobe Acrobat PDF | View Details Download |