• Posted March 24, 2023

Million-Person Study Finds Genes Common to Many Addiction Disorders

Breakthrough research shows genetic markers for substance abuse and could lead to more effective ways to prevent and treat drug and alcohol use disorders.

These findings could help people who face addiction to varied substances, including those who have more than one addiction at a time.

The findings also reinforce the role of the dopamine system in addiction. Dopamine is a chemical messenger in the brain involved in reward, motivation and anxiety, among other things.

The combination of genes underlying addiction disorders was associated with regulation of dopamine signaling, the study found.

Dr. Nora Volkow, director of the U.S. National Institute on Drug Abuse, said genetics play a key role in determining health but are not destiny.

"Our hope with genomic studies is to further illuminate factors that may protect or predispose a person to substance use disorders -- knowledge that can be used to expand preventative services and empower individuals to make informed decisions about drug use,"she said in a news release from the U.S. National Institutes of Health.

"A better understanding of genetics also brings us one step closer to developing personalized interventions that are tailored to an individual's unique biology, environment, and lived experience in order to provide the most benefits,"Volkow explained.

To better understand substance use disorders, researchers combed through the genomic data of more than 1 million people.

Substance use disorders can be passed along genetically and are influenced by complex gene interactions.

The researchers use a method called genome-wide association to try to identify specific genes involved in various disorders. It involves searching genomes for regions of variation -- called single-nucleotide polymorphisms (SNPs) -- associated with the same disease, disorder, condition or behavior among multiple people.

Using this method, the investigators pinpointed areas in the genome associated with general addiction risk, as well as specific risk involving alcohol, nicotine, cannabis and opioids.

The sample included more than 1 million people of European ancestry and more than 92,000 of African ancestry, as determined by their genes.

"Using genomics, we can create a data-driven pipeline to prioritize existing medications for further study and improve chances of discovering new treatments,"lead study author Alexander Hatoum explained. He's a research assistant professor at Washington University in St. Louis.

Hatoum and his team found 19 SNPs that were significantly associated with general addiction risk in the European ancestry sample and 47 SNPs for specific substance disorders.

The strongest gene signals consistent across various disorders came from areas in the genome known to control dopamine signaling, the study authors said. That suggests that genetic variation in dopamine signaling regulation is key to addiction risk.

The genomic pattern identified also predicted having two or more substance use disorders at once, according to the study.

It was also a predictor of higher risk of mental and physical illness, including psychiatric disorders, suicidal behavior, respiratory disease, heart disease and chronic pain conditions.

In 9- and 10-year-old children with no experience of substance use, these genes correlated with parental substance use and externalizing behavior. (Examples of externalizing behaviors include assault, lying and truancy.)

"Substance use disorders and mental disorders often co-occur, and we know that the most effective treatments help people address both issues at the same time," said Dr. Joshua Gordon , director of the U.S. National Institute of Mental Health. "The shared genetic mechanisms between substance use and mental disorders revealed in this study underscore the importance of thinking about these disorders in tandem."

Unlike the analysis of the European sample, which linked many SNPs to addiction risk, the analysis of the African ancestry sample found only one SNP associated with general addiction risk and one substance-specific SNP for risk of alcohol use disorder.

The researchers said this underscores disparities in availability of data from globally representative populations that must be addressed.

"The current study validates previous findings of alcohol-specific risk variants and, importantly, makes this finding in a very large and more diverse study population," said National Institute on Alcohol Abuse and Alcoholism Director George Koob.

The finding of shared genetic risk variants provides insight into the mechanisms that underlie these disorders and their relationships with other mental health conditions, Koob added.

"Together the findings of alcohol-specific risk variants and common addiction-related variants provide powerful support for individualized prevention and treatment,"he said.

In the United States, 46 million people aged 12 and up had at least one substance use disorder in 2021. About 107,000 people died of drug overdoses.

The study findings were published March 22 in Nature Mental Health.

More information

The U.S. Centers for Disease Control and Prevention has more on drug overdoses and deaths.

SOURCE: U.S. National Institutes of Health, news release, March 22, 2023