People have the same general set of genes, but at the sequence level, many small variations between individuals exist. Genome-wide association studies search for specific variants that are linked to particular characteristics or traits. New work reported in Biological Psychiatry utilized data from 30,000 people that had been exposed to opioids to look for gene variants that are connected to opioid dependence. Their investigation found one and may now help open up a new avenue for treatment.
"It's widely recognized that we need a better understanding of the biological influences on opioid use; it is possible that biological understanding can lead to treatments," explained the senior author of the report, Joel Gelernter, M.D., of Yale University.
The United States is in the throes of an opioid crisis. The Centers for Disease Control is trying to learn more about the problem. They found a recent jump in overdoses after analyzing emergency room visits between July 2016 and September 2017. That data included 142,557 incidents that were thought to be opioid overdoses.
This genetic assessment, noted John Krystal, M.D., Editor of Biological Psychiatry, provides some insight into the risk factors for dependence. To this point, the role of genetics has been hard to find because of the complex interplay of the environment with genetic influences, as well as how drug availability further confounds the results.
To identify some of the ways that genetics contribute to opioid dependence, first author Zhongshan Cheng, Ph.D., and the research team scanned the whole genome, searching for genetic factors. In the study, there were 3,058 European-American patients who were exposed to opioids; 1,290 met criteria that diagnosed opioid dependence. Instead of taking into account the presence or absence of a diagnosis, this patient analysis looked at how severe the opioid dependence was, using a number of different parameters met by the individual when receiving the clinical diagnosis.
In the end, one specific change was identified. "If you have a certain RGMA variant, you're more likely to have opioid dependence symptoms than if you have the alternative form," explained Dr. Gelernter.
In addition, RGMA was associated with several genes that are vital to normal brain function and have been connected to other brain disorders like autism, schizophrenia, and Alzheimer's disease.
To follow up on their findings and look for how exactly the gene plays into drug dependence, the research team analyzed how morphine impacted the amount of protein produced by the RGMA gene in a mouse model. They found that levels of Rgma protein increased during chronic morphine treatment. Previous work has indicated that the Rgma protein controls nerve growth and cell death in the brain. This provides researchers with some insight into how the gene might impact how the brain responds to opioids.
"We believe this is a good new lead and hope it encourages novel pharmacological approaches to treating opioid dependence," said Dr. Gelernter.