A new human genomics study led by Yale scientists has identified genetic risk factors for opioid use disorder (OUD) and related substance use disorders according to a new large-scale genome-wide association study — increasing the number of known risk genes from 1 to 19.
This work comes at a time when opioid-related overdoses have reached an all-time high in the United States and continue to rise around the world. The findings, published in Molecular Psychiatry, addressing an urgent need, as genetic discovery for OUD has been limited in recent years. Genetic discovery leads to a better understanding of biology.
Senior author Joel Gelernter, MD, Foundations Fund professor of psychiatry and professor of genetics and neuroscience at Yale, said not much is known about specific genetic factors that influence the risk of OUD. In this study, researchers worked to increase the knowledge of OUD genetics through an a meta-analysis for OLD – that is, compiling data from many different studies – and then by including genetic information of other related disorders in the use of resources for increased gene-finding ability.
Researchers investigated genetic data of more than 600,000 participants of European and African genetic descent, more information than previous studies on OLD risk variation. The scientists identified genetic variation in 19 genes that was associated with OUD risk; OPRM1 and FURIN were two genes identified in the analysis of OUD alone, with many more genes identified in the analysis that included information from OUD along with cannabis use disorder and alcohol use disorder.
“OPRM1 is a gene that encodes mu opioid receptors in the brain, making it an excellent genetic opportunity for OUD – previous work showed that variation in this gene influences OUD risk. Our challenge was to go beyond OPRM1,” Gelernter said.
“Our effort yielded as much genome-wide data as possible. We wanted to collect as many data sets and samples as possible,” said Joseph D. Deak, Ph.D., postdoctoral fellow in the Yale Department of Psychiatry Division of Human. Genetics and the first author of the paper. “We believe that our findings have identified genetic risk specific to OUD, as well as genetic risk that is more broadly shared with other types of substance use disorders. That is consistent with previous studies showing specific genetic effects for certain drugs, along with shared genetic liability for substance use disorders in general.”
The findings also reveal genetic links between the development of OUD and related conditions such as: chronic pain, the inability to work because of an illness or disability, and other psychiatric outcomes such as anxiety, depression, and PTSD. “These genetic findings are consistent with common features often seen in the clinical presentation of individuals diagnosed with OLD. We found that genetic overlap,” Deak said.
We know that there are many factors that influence the risk of substance use disorders, such as OLD. These results do not indicate that someone with this specific genetic risk factors whether or not to prescribe opioids to control pain or the like; this work does not support that conclusion, but it could help clarify some unanswered questions as we continue to expand on these findings in hopes of addressing public health concerns related to opioids.
Joseph D. Deak et al. Genome-wide association study in individuals of European and African descent and multi-trait analysis of opioid use disorder identifies 19 independent genome-wide significant risk loci, Molecular Psychiatry (2022). DOI: 10.1038/s41380-022-01709-1
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