The study found common genetic risk variants across various substance use disorders

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By combing through the genetic data of more than a million people, scientists have identified genes commonly inherited across addiction disorders, regardless of the substance used. This dataset–one of the largest of its kind–may help uncover new treatment targets across many substance use disorders, including in people diagnosed with more than one. The findings also reinforce the role of the dopaminergic system in addiction, by showing that the combination of genes underlying addictive disorders was also associated with the regulation of dopamine signaling.

Posted today in The nature of mental healthThe study was led by researchers at Washington University in St. Louis, along with more than 150 co-authors from around the world. It was supported by the National Institute on Drug Abuse (NIDA), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute of Mental Health (NIMH), and Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute on Aging.

There has been limited knowledge of the molecular genetic underpinnings of addiction to date. Furthermore, most clinical trials and behavioral studies have focused on individual substances, rather than addiction on a larger scale.

“Genes play a major role in determining health throughout our lives, but they are not destiny. We hope that through genetic studies we can shed more light on factors that may protect or predispose a person to substance use disorders – knowledge that can be used to expand preventive services and empower individuals to make informed decisions.” “A better understanding of genetics brings us one step closer to developing personalized interventions that are tailored to an individual’s unique biology, environment, and living experience in order to provide the greatest benefits.”

In 2021, more than 46 million people in the United States ages 12 or older had at least one substance use disorder, and only 6.3% had received treatment. Furthermore, people who use drugs are faced with an increasingly dangerous drug supply, often tainted with fentanyl. Nearly 107,000 people died from drug overdoses in 2021, and 37% of those deaths involved simultaneous exposure to both opioids and stimulant medications. Drug use and addiction is a public health crisis characterized by high social, emotional and financial costs to families, communities and society.

Substance use disorders are genetic and influenced by complex interactions between multiple genes and environmental factors. In recent decades, a data-rich method, called genome-wide association, has emerged to try to identify specific genes involved in specific disorders. This method involves searching entire genomes for regions of genetic variation, called single-nucleotide polymorphisms (SNPs), that are associated with the same disease, disorder, condition or behavior among several people.

In this study, the researchers used this method to identify regions in the genome associated with general addiction risk, as well as risk for substance use disorders — such as alcohol, nicotine, cannabis, and opioid use disorders — in a sample of 1,025,550 individuals. with genes indicating European ancestry and 92,630 individuals having genes indicating African ancestry.

“Using genomics, we can create a data-driven pipeline to prioritize existing drugs for further study and improve the chances of discovering new therapies. To do this accurately, it is critical that the genetic evidence we collect include universally representative cohorts and that we have members,” Alexandre Hatoum said. Louis, Ph. D., research assistant professor at Washington University in St. Louis and lead author of the study, said the communities have historically been underrepresented in the biomedical research that drive and contribute to these types of studies.

Hatoum and the research team discovered different molecular patterns that underlie addiction, including 19 independent SNPs significantly associated with general addiction risk and 47 SNPs for substance-specific disorders among a sample of European ancestry. The strongest consistent gene signaling across different disorders maps to regions in the genome known to control the regulation of dopamine signaling, suggesting that genetic variation in the regulation of dopamine signaling, rather than dopamine signaling itself, is central to addiction risk.

Compared to other genetic predictors, the genotype identified here was also a more sensitive predictor of the presence of two or more substance use disorders simultaneously. The genomic pattern also predicted a higher risk of mental and physical illnesses, including psychiatric disorders, suicidal behavior, respiratory disease, heart disease, and chronic pain conditions. In 9- or 10-year-olds without any substance abuse experience, these genes were associated with parental substance use and outside behavior.

Substance use disorders and mental disorders often occur together, and we know that the most effective treatments help people address both issues at the same time. The shared genetic mechanisms between drug use and mental disorders revealed by this study underscore the importance of considering these disorders in tandem.”


Joshua A. Gordon, MD, PhD, director of NIMH

Genomic analysis in the African ancestry sample revealed one SNP associated with general addiction risk and one substance-specific SNP for alcohol use disorder risk. The paucity of results here underscores persistent disparities in data inclusion for globally representative populations that must be addressed to ensure data robustness and accuracy, note Hatoum and co-authors.

Inclusion of data from different ancestral populations in this study cannot and should not be used to assign or categorize variable genetic risks for substance use disorder to specific populations. As genetic information is used to better understand human health and health disparities, extensive and comprehensive data collection is essential. NIDA and other institutes within the National Institutes of Health supported a recent report on the responsible use and interpretation of genomic data at the population level by the National Academies of Sciences, Engineering, and Medicine. See also a similar statement from the National Institutes of Health.

While Hatoum and her colleagues identified a genotype that indicates widespread addiction risk, they note that diagnoses of drug use still make sense. NIAAA Director George F. Cobb, PhD: “The current study validates previous findings for risk variables for alcohol and, more importantly, brings this finding into a very large and more diverse cohort of study.” “The discovery of genetic risk variants shared across various substance use disorders provides insight into some of the mechanisms that underlie these disorders and the relationships with other mental health conditions. Together, the findings of alcohol-specific risk variants and common addiction-related variants provide support for individualized prevention and treatment.”

source:

Journal reference:

Hatoum A. et al. (2023). A genome-wide multivariate association meta-analysis of more than 1 million people identifies loci underlying multiple drug use disorders. The nature of mental health. doi.org/10.1038/s44220-023-00034-y

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