Unraveling the Genetic Threads of Substance Use Disorders
By Lauren DeSouza- Master of Public Health, Simon Fraser Public Research University – Canada
Staff Research and Content Writer
© Copyright – SUD RECOVERY CENTERS – A Division of Genesis Behavioral Services, Inc., Milwaukee, Wisconsin – June 2023 – All rights reserved.
Genetics plays a key role in determining our health throughout our lives. Genetics is a powerful and consistent predictor of both physical and mental disorders. For example, certain genetic factors can predispose people to substance use disorders, including tobacco use disorder, cannabis use disorder, alcohol use disorder, and opioid use disorder. In fact, family history is the single most reliable indicator of risk for future substance abuse.
A recent study discovered a shared genetic sequence in individuals with different substance use disorders. Those with this genetic sequence are more likely to develop any type of substance use disorder. These findings could pave the way for new treatments that can target multiple addictions.
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How do genetics influence SUD risk?
The risk of developing a substance use disorder (SUD) is strongly linked to genetics. If someone has a family history of SUDs, they may have a genetic predisposition to develop one as well. However, having this genetic predisposition does not necessarily mean they will develop an addiction in their lifetime; environmental factors also impact a person’s overall risk of developing an addiction.
The genetic signature associated with addiction is linked to how the brain regulates dopamine. The brain’s reward system relies heavily on dopamine, and addiction often stems from the spikes in dopamine caused by substance use. Repeated exposure to addictive substances alters how the reward system responds to dopamine, requiring more and more of the substance to achieve the same reward. While the link between dopamine and SUDs is well-established, this study provides more specific insights into the neuronal pathways affected by addiction.
How did this study work?
Researchers analyzed the genomic data of over 1.1 million individuals with SUDs, one million Caucasian individuals and 92,000 African individuals. They identified variations in the genome that were closely associated with specific SUDs and with general addiction. The large sample size enabled the researchers to find genetic variations associated with a higher risk of having one or multiple SUDs.
The researchers uncovered the specific pathways through which the brain controls its reaction to substance-induced dopamine signalling. This discovery could lead to treatments that modify the brain’s response to dopamine signalling induced by substances, which could help prevent or reverse addiction.
The authors were also interested in medications that could use this genetic information to more accurately target addiction pathways. They compiled a list of over 100 approved and investigational pharmaceutical drugs that could be repurposed to treat SUDs, including those that can influence how the brain regulates dopamine signalling.
What were the main findings?
The researchers identified a genetic sequence that was common among people with various SUDs. This genetic sequence includes 19 single-letter differences in the DNA code that are significantly associated with general addiction risk. It also contains 47 genetic variants linked to specific substance disorders — nine for alcohol, 32 for tobacco, five for cannabis and one for opioids
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Separately, the genomic analysis of individuals of African ancestry showed only one genetic variation associated with general addiction risk and one substance-specific variation for the risk of alcohol use disorder. The researchers note that these minimal findings may be due to the much smaller sample size of African individuals included in the study. They emphasized the need to address these data disparities and diversify the data collection in genetics research.
The genetic sequence for addiction was also connected to polysubstance disorder and a higher risk of developing other medical conditions, including psychiatric illnesses, self-harming behaviours, and chronic conditions arising from problematic substance use (e.g., chronic airway obstruction) or that predict problematic substance use. (e.g., chronic pain).
What are the implications of this research?
This study represents a significant advance in understanding how genetic factors predispose people to substance use disorders. Most notable is the discovery that a general addiction genetic factor conveys vulnerability to multiple SUDs. Most medications to treat SUDs target the use of a specific substance, such as tobacco or opioids, but polysubstance use is common among people with SUDs. Thus, the shared genetic sequence identified in this study could inform the development of universal treatments for multiple addictions. Exiting medications that target this genetic sequence can be repurposed to treat polysubstance use.
The authors also emphasize the importance of these findings in substance use prevention efforts. By highlighting how SUDs can be passed down genetically, individuals will be more empowered to make informed decisions about their substance use.
- A person’s genetics can predispose them to developing a substance use disorder.
- A new study uncovered a genetic sequence common amongst individuals with any type of substance use disorder.
- This genetic sequence offers possibilities to better treat those with substance use disorders, most notably those who use multiple substances.
Addiction Policy Forum. (May 24, 2023). “Study Finds Inherited Genetic Signature Linked to Increased Risk for Addiction.
Hatoum, A.S., Colbert, S.M.C., Johnson, E.C. et al. Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders. Nat. Mental Health 1, 210–223 (2023).
Strait, J.E. (March 22, 2023) “Multiple substance use disorders may share inherited genetic signature.” Washington School of Medicine in St. Louis News Hub.