Multi-species convergent functional genomics analysis of substance usedisorders reveals shared genes in poly-drug use

Bailey E. West

Document Type

Article

Publication Date

Summer 2021

JAX Location

In: Student Reports, Summer 2021, The Jackson Laboratory

Abstract

Substance use disorder is a highly complex and prevalent disease, often involving the use of multiple addictive substances. While it is known that genetic influences can predispose individuals to addiction, the precise polygenic underpinnings of polysubstance use are poorly understood. We hypothesize that some genes involved in specific substance use disorders may also have shared involvement in polysubstance use. Using the computational tool GeneWeaver, we curated sets of genes from a wide range of current literature spanning various data types, drugs, and species and integrated these data to identify genes that are associated with multiple substance use phenotypes including use of amphetamines, cocaine, cannabinoids, and opioids.We found that several addiction-related genes are indeed implicated in multiple drug types, with cocaine and opioids sharing the highest gene overlap with each other out of the pairwise drug-drug comparisons. However, the inclusion of gene sets derived from Medical Subject Headings(MeSH) terms may bias the analysis toward genes that are already well-known in addiction biology, and cocaine and opioids have the most data available on GeneWeaver. These results suggest shared biological addiction mechanisms between different substance use disorders, which will be important for developing generally useful therapies in the future.

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