Tuesday, Aug. 25, 2020
Collaborative efforts by a group of researchers at Virginia Commonwealth University’s Alcohol Research Center have led to major advances toward understanding the genetic components of alcohol related disorders, according to the center’s director, Michael Miles, M.D., Ph.D.
Now, with the help of a recent $7.8 million grant renewal from the National Institute on Alcohol Abuse and Alcoholism, a division of the National Institutes of Health, researchers hope to gain even greater perspective on the links between genetics and alcohol use disorder, which includes abusive alcohol consumption.
The VCU Alcohol Research Center, a multidisciplinary center that focuses on pre-clinical and clinical studies to advance the understanding and root cause of alcohol misuse and alcoholism, was established in 2009 through the support of a National Institutes of Health grant. The collaborative effort among researchers continued in 2014 when the National Institute on Alcohol Abuse and Alcoholism awarded VCU a five-year grant to expand the center.
“We had the idea that, by bringing a group together that all used genetics but did it across different disciplines and models, we could potentially get at the real complexity of how alcohol changes the nervous system and eventually causes someone to be addicted to alcohol,” said Miles, the grant’s lead researcher and a professor of pharmacology, toxicology and neurology at the VCU School of Medicine.
From the center’s earlier work, researchers have determined that about half of alcohol addiction is attributed to social and environmental factors, while the other half is genetic. However, finding the genes that influence alcohol addiction is difficult since there are many genes contributing, each only a small portion of the overall risk. The center is working to identify key genes that influence risk for alcohol addiction and may also lead to future therapeutics.
“Perhaps if we can identify a key gene that controls a network of genes that has a certain impact on alcohol behaviors, we may actually be able to give clues about new therapeutic agents,” Miles said.
How genes play a role in alcohol addiction
One promising area of the Alcohol Research Center’s work is a particular way that the body communicates information to the brain and the role that communication plays in addiction. Researchers at the center found that genetic variation in a network of genes around a specific protein was higher among those with alcohol dependence. The findings suggested that a drug that inhibits this protein could reduce a person’s alcohol consumption.
The team has discovered several genes that play a role in alcohol addiction, but the topic is complicated, Miles said. Just because someone has some of these genetic risk markers does not mean the person is going to become an alcoholic, he explained. It just means the person has a higher probability of having an alcohol addiction. Additionally, Miles said, there likely will not be a single genetic marker that tells the whole story.
“It could be a panel of genes that might tell us that a person has a certain higher percent risk of becoming an alcoholic,” he said.
The research has social implications, as alcohol addiction is a major public health concern. A Centers for Disease Control and Prevention study found that the cost of excessive alcohol use in the United States reached $249 billion in 2010, mostly from binge drinking. The costs were caused by lost workplace productivity, health care costs, criminal justice expenses and motor vehicle crashes.
In addition, the center’s researchers have published studies on the link between alcohol use disorder and suicide and have organized symposiums on substance use disorders and young people, among other projects.
We had the idea that, by bringing a group together that all used genetics but did it across different disciplines and models, we could potentially get at the real complexity of how alcohol changes the nervous system and eventually causes someone to be addicted to alcohol.
‘We’re using a range of tools’
Miles said the center’s research also has implications for other types of addictions. A better understanding of how the brain changes due to alcohol addiction could help inform researchers about the body’s interactions with drugs such as cocaine or opioids.
“There's a lot of molecular events that are similar across drugs of abuse, and the neurobiology has certain similarities,” Miles said.
He and the team hope the latest funding will allow for further research that gives scientists a greater understanding of how the brain works, how health care providers define alcoholism and how they treat it.
Kenneth S. Kendler, M.D., director, professor and eminent scholar at the Virginia Institute for Psychiatric and Behavioral Genetics at VCU, is an active partner with Miles in the research and was the lead on the effort for the previous five-year funding cycle. Kendler, the center’s scientific director, sees the potential for great advances from the work.
“The very broadest picture is: We’re using a range of tools to try to clarify the complexity of the transmission of drug and alcohol prevention [and] effects through families,” Kendler said.
“Part of what we’ve been interested in is understanding the role of genetic, but also non-genetic, factors in transmission,” Kendler said. “We know, for example … you can learn [behaviors related to drug and alcohol addiction] from your relatives — both from your siblings and from spouses. We’ve tried to take advantage of natural experiments — such as Swedish population registries — to understand causal factors within addiction and drug abuse.”
Peter Buckley, M.D., interim CEO of VCU Health System, interim senior vice president of VCU Health Sciences and dean of the School of Medicine, emphasized the importance of this work to the medical field’s understanding of how to treat substance use disorders.
“The work of our team members at the Alcohol Research Center and across this university and health system to address addiction is foundational for finding new treatments for alcohol use disorder and other diseases stemming from substance abuse,” Buckley said. “Their continued work will help many more people who battle addiction every day.”
In addition to Kendler and Miles, lead investigators of individual projects or cores at the Alcohol Research Center include researchers from multiple departments at VCU: Fazil Aliev, Ph.D., a research associate in the Department of Psychiatry; James Bjork, Ph.D., associate professor of psychiatry; Silviu-Alin Bacanu, Ph.D., associate professor of psychiatry; Jill Bettinger, Ph.D., professor of pharmacology and toxicology; Andrew Davies, Ph.D., assistant professor of pharmacology and toxicology; Danielle Dick, Ph.D., professor of psychology; Mikhail Dozmorov, Ph.D., associate professor of biostatistics; Alexis Edwards, Ph.D., associate professor of psychiatry; Michael Grotewiel, Ph.D., professor of human and molecular genetics; Brien Riley, Ph.D., professor of psychiatry; Joel Schlosburg, Ph.D., assistant professor of pharmacology and toxicology; B. Todd Webb, Ph.D., assistant professor of psychiatry; Jennifer Wolstenholme, Ph.D., assistant professor of pharmacology and toxicology.
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