Talk to the Veterans Crisis Line now
U.S. flag
An official website of the United States government

VA Health Systems Research

Go to the VA ORD website
Go to the QUERI website

HSR Citation Abstract

Search | Search by Center | Search by Source | Keywords in Title

Cross-ancestry meta-analysis of opioid use disorder uncovers novel loci with predominant effects in brain regions associated with addiction.

Kember RL, Vickers-Smith R, Xu H, Toikumo S, Niarchou M, Zhou H, Hartwell EE, Crist RC, Rentsch CT, Million Veteran Program, Davis LK, Justice AC, Sanchez-Roige S, Kampman KM, Gelernter J, Kranzler HR. Cross-ancestry meta-analysis of opioid use disorder uncovers novel loci with predominant effects in brain regions associated with addiction. Nature neuroscience. 2022 Oct 1; 25(10):1279-1287.

Dimensions for VA is a web-based tool available to VA staff that enables detailed searches of published research and research projects.

If you have VA-Intranet access, click here for more information vaww.hsrd.research.va.gov/dimensions/

VA staff not currently on the VA network can access Dimensions by registering for an account using their VA email address.
   Search Dimensions for VA for this citation
* Don't have VA-internal network access or a VA email address? Try searching the free-to-the-public version of Dimensions



Abstract:

Despite an estimated heritability of ~50%, genome-wide association studies of opioid use disorder (OUD) have revealed few genome-wide significant loci. We conducted a cross-ancestry meta-analysis of OUD in the Million Veteran Program (N? = 425,944). In addition to known exonic variants in OPRM1 and FURIN, we identified intronic variants in RABEPK, FBXW4, NCAM1 and KCNN1. A meta-analysis including other datasets identified a locus in TSNARE1. In total, we identified 14 loci for OUD, 12 of which are novel. Significant genetic correlations were identified for 127 traits, including psychiatric disorders and other substance use-related traits. The only significantly enriched cell-type group was CNS, with gene expression enrichment in brain regions previously associated with substance use disorders. These findings increase our understanding of the biological basis of OUD and provide further evidence that it is a brain disease, which may help to reduce stigma and inform efforts to address the opioid epidemic.





Questions about the HSR website? Email the Web Team

Any health information on this website is strictly for informational purposes and is not intended as medical advice. It should not be used to diagnose or treat any condition.