A large multicenter study reveals the existence of shared genetic markers underlying drug addiction
Shared genetic markers underlie drug addiction, large multi-center study reveals These groundbreaking findings could lead to more effective prevention and treatment strategies for multiple substance use disorders. By analyzing the genomic data of more than one million people, researchers have identified the genes most often inherited in addictive disorders, regardless of the substance used. This data collection, one of the largest of its kind, could help find new treatment targets for various substance use disorders, even for people who abuse more than one substance. The findings also strengthen the role of the dopaminergic system in addictions, also demonstrating that the combination of genes underlying addictive disorders is associated with the activity of the dopamine system.
The study, published in Nature Mental Health, was conducted by researchers at Washington University in St.Louis, together with 150 other co-authors from around the world, and coordinated by the National Institute on Drug Abuse (NIDA). “Until now, knowledge about the genetic and molecular basis of drug addiction was limited. Additionally, most of the clinical and behavioral studies had focused on single substances, rather than addictions more broadly,” says NIDA director Nora Volkow. «Instead, genetics plays a key role in determining health throughout life, but it is not an inescapable destiny. With genomic studies we hope to further elucidate the factors that may predispose a certain person to substance abuse or protect them from it. This knowledge can be used to expand prevention services and enable people to make more informed decisions about drug use. A deeper understanding of genetics will help us develop interventions tailored to an individual’s biology, environment and background to deliver the greatest benefits.”
In 2021, more than 46 million people ages 12 and older in the United States were abusing at least one substance, and only a tiny percentage of them had received treatment. Furthermore, for drug addicts, drug supply is an increasingly dangerous matter, as today’s drugs of abuse are often cut with fentanyl (a synthetic opioid used as an anesthetic). Also in the USA in 2021 over 100 thousand people died from overdoses, which in 37% of cases was caused by simultaneous exposure to opioids and stimulants. In Italy the numbers, in relation to the population, are similar. Drug use and addiction are a serious public health issue, with heavy emotional implications and high socio-economic costs for families, communities and society. Substance use disorders are heritable and influenced by complex interactions between multiple genes and environmental factors.
In recent decades, an innovative method, called “genome-wide association”, has emerged to try to identify specific genes involved in certain disorders. In this study, the researchers used this method on a sample of more than one million individuals of European ancestry and nearly 100,000 individuals of African ancestry to identify areas in the genome associated with general addiction risk, as well as risk for specific drug abuse disorders. substances (alcohol, nicotine, cannabis and opioids). “Using genomics, a line of research can be implemented that prioritizes existing drugs, but also other studies aimed at discovering new treatments.
To do all of this accurately, it is crucial to collect genetic evidence that is globally representative even of historically underrepresented populations in biomedical research,” says Alexander Hatoum, lead author of the study. “The findings of these researches could revolutionize current prevention strategies and pave the way for more effective treatments for more abuse disorders.” Hatoum and his research team at Washington University in St. Louis found 19 gene variations significantly associated with generic risk of drug addiction and another 47 associated with specific substance abuse in a population of European ancestry.
The strongest and most common gene variations in various addictions have been mapped on areas of the genome responsible for controlling dopamine synthesis, suggesting a fundamental role for this neurotransmitter for the risk of addiction. Compared with other predictors, dopamine gene variation was also a sensitive predictor of being able to have two or more substance use disorders concurrently. This gene model also predicted a higher risk of mental and physical illnesses, including psychiatric disorders, suicidal behavior, respiratory disease, heart disease and chronic pain. In children aged 9 to 10 with no substance use experience, these genes were related to parental substance abuse and externalizing behaviors. “Substance use disorders and mental disorders often occur together, and the most effective treatments are known to help people deal with both at the same time. The shared gene alterations from substance abuse and mental disorders highlighted by this study underscore the importance of thinking about these disorders in tandem,” said Joshua A. Gordon, director of the National Institute of Mental Health (NIMH).
Genomic analysis in the sample of African ancestry revealed one gene variation associated with generic drug addiction risk and another specific for alcohol abuse risk. “The paucity of results for the African-descended population in this study underscores current disparities in data inclusion at the representativeness level of global populations, which need to be addressed to ensure data robustness and accuracy,” Hatoum and co-authors note. . However, the inclusion of data from different ancestral groups in this study cannot and should not be used to assign or rank the genetic risk variable for substance use disorders for specific populations. However, as genetic information is used to better understand human health and health inequalities, expansive and inclusive data collection is essential.
Although Hatoum and colleagues have identified gene patterns that indicate broad addiction risk, they note that they are specific to substance abuse and that clinical diagnoses retain their significance. “The current study validates previous findings of alcohol-specific risk variants and, importantly, confirms this finding in a very large and diverse study population,” said George F. Koob, director of the National Institute on Alcohol Abuse and Alcoholism. NIAAA). “The finding of shared genetic risk variants across several substance use disorders provides insight into some of the mechanisms underlying these disorders and their relationships to other mental health disorders. Taken together, the indications relating to alcohol-specific risk variants and generic drug addiction risk variants provide powerful support for new individualized prevention and treatment strategies.
April 1, 2023 (change April 1, 2023 | 14:07)
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