New Gene Variant Robustly Linked to Opioid Addiction

Megan Brooks
March 01, 2018

Researchers have identified a novel gene variant involved in opioid addiction, a finding that may aid efforts to develop novel pharmacologic approaches to the treatment of opioid dependence.

In a genome-wide association study, investigators found that a variant on chromosome 15 (rs12442138) near the repulsive guidance molecule A (RGMA) gene was associated with opioid dependence at a "genome-wide significant" level.

"We hope that this new biology that we identified will lead to new treatment strategies. Previously, there was little reason to focus on RGMA systems in developing opioid dependence treatments. Now there is," senior author Joel Gelernter, MD, professor of psychiatry and director of the Division of Human Genetics in Psychiatry, Yale University, New Haven, Connecticut, told Medscape Medical News.

The study was published online January 11 in Biological Psychiatry.

Promising Lead

Opioid dependence is a genetically complex disorder that is influenced by complex environmental factors, making it tough to identify genetic factors that underlie the disorder, Gelernter and colleagues note in their article.

To tease out some of the genetic contributions to opioid dependence, they scanned the genomes of 3058 opioid-exposed European Americans, including 1290 who met DSM-IV criteria for opioid dependence.

They found that the rs12442183 variant near the RGMA gene had a "robust" association with opioid dependence. "If you have a certain RGMA variant, you're more likely to have opioid dependence symptoms than if you have the alternative form," Gelernter said.

"We believe this is a good new lead and hope it encourages novel pharmacological approaches to treating opioid dependence," Gelernter told Medscape Medical News. He added that larger opioid dependence clinical samples are needed to replicate and extend the current findings.

This RGMA variant was also linked to opioid dependence in a group of African Americans, but the association was much weaker than in European Americans.

Prior studies have shown that the protein product of RGMA regulates cell death and nerve growth in the brain, findings that suggest how the gene might alter the brain's response to opioids, the researchers point out.

In an analysis of brain tissue expression datasets, they further demonstrated a significant correlation between the expression of RGMA and the expression of four genes that have been shown to affect risk for other psychiatric disorders, including schizophrenia, Alzheimer's disease, and autism.

"These RGMA coexpressed genes are critical to normal brain function, supporting the potential involvement of RGMA in related biological processes," the researchers conclude.

"In the midst of an opioid crisis, it is timely to identify new genetic risk factors that contribute to addiction risk," John Krystal, MD, chairman, Department of Psychiatry, Yale University School of Medicine, and editor of Biological Psychiatry, commented in a news release.

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SOURCE: March 01, 2018. Biol Psychiatry. Published online January 11, 2018.

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