Research Uncovers Common Genetic Indicators Linked to Substance Abuse Disorders

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Over 46 million people in the US in 2021, aged 12 or older, had at least one substance use disorder with less than 7 percent receiving treatment. In the field of behavioral health and among many people alike, there’s a pervasive misunderstanding about addiction, supported by the DSM-5 that refers to addiction spectrum disorders as Substance Use Disorders, categorized by one of 11 substances that DSM-5 considers as separate diagnoses.

For example, if a person has addiction marked by loss of control and continued use despite adverse consequences related to using alcohol, stimulants and caffeine, they receive three different Substance Use Disorders diagnoses, according to DSM-5. This leads to the misunderstanding that addiction is caused by the different  substance rather than addiction being a primary brain disease that exists before drug use but only manifests with drugs once a certain amount of drug for a certain amount of time is used for any given person. This preexisting state leaves certain genetically vulnerable people susceptible to developing addiction involving many different substances and behaviors, and has now been shown to be associated with certain genetic markers. 

In a massive, new study published in Nature Mental Health researchers used data from more than one million people and identified genes commonly inherited across addiction disorders, regardless of the specific substance(s) being used. 

Historically, we’ve known little about the molecular genetic underpinnings of addiction broadly since studies have targeted individual substances (or specific Substance Use Disorders) versus looking at genome-wide associations for addiction at large. The research is even more limited when we include behavioral addictions in the mix with addiction involving ingestion of substances.

When we know more about any given individual’s risk level based on their genetic loading (which this study examined) and adverse life experiences, we are better equipped to initiate preventive services to at-risk populations. Studies like these can be used to develop new treatment options along biological, psychosocial and spiritual modalities that can be tailored to individuals in culturally relevant ways. 

The Research

The study was led by a who’s who of researchers at Washington University in St. Louis, along with more than 150 co-authors from around the world. Additionally, 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), the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute on Aging.

The researchers identified genomic regions linked to the overall risk of addiction, as well as the risk of specific substance use disorders, such as alcohol, nicotine, cannabis, and opioid use disorders. The study analyzed the genetic information of 1,025,550 people with European ancestry and 92,630 individuals with African ancestry.

“Using genomics, we can create a data-driven pipeline to prioritise existing medications for further study and improve chances of discovering new treatments,” said Alexander Hatoum, PhD., one of the study’s lead researchers. 

Key Findings 

The Dopamine System

The results reinforce the significance of the dopamine system in addiction, as they demonstrate that the group of genes linked to addiction spectrum disorders is also connected to the control of dopamine signaling.

European Ancestry Sample

  • The researchers discovered various molecular patterns underlying addiction, including 19 independent single-nucleotide polymorphism (SNPs) significantly associated with general addiction risk and 47 SNPs for specific substance disorders.
  • The strongest gene signals consistent across the various disorders mapped to areas in the genome known to control regulation of dopamine signaling, suggesting that genetic variation in dopamine signaling regulation, rather than in dopamine signaling itself, is central to addiction risk.
  • The identified genomic pattern in this study was more effective in predicting the occurrence of two or more simultaneous substance use disorders.
  • This pattern also indicated a greater likelihood of both mental and physical health issues, encompassing psychiatric disorders, suicidal tendencies, respiratory ailments, heart disease, and chronic pain conditions.

African Ancestry Sample

  • The genetic analysis of the African ancestry sample identified one SNP related to overall addiction risk and another SNP specifically linked to the risk of alcohol use disorder. 
  • The scarcity of findings in this area highlights the continuing inequality in the representation of diverse populations in data collection.

The researchers stressed that incorporating data from various ancestral backgrounds in this study should not be employed to allocate or classify varying genetic risks for substance use disorder among specific populations. As we utilize genetic information to enhance our understanding of human health and health disparities, it is crucial to gather data in a comprehensive and inclusive manner.

“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,” said NIDA Director, Nora Volkow, M.D. “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.”