New NIH study reveals shared genetic markers underlying substance use disorders
Breakthrough findings could lead to more effective prevention and
treatment strategies for multiple substance use disorders

Date:
March 22, 2023
Source:
NIH/National Institute on Drug Abuse
Summary:
By combing through genomic data of over 1 million people of
European or African descent, scientists have identified genes
commonly inherited across addiction disorders, regardless of
the substance being used. This dataset -- one of largest and most
diverse of its kind -- may help reveal new treatment targets across
multiple substance use disorders, including for people diagnosed
with more than one. The findings also reinforce the role of the
dopamine system in addiction, by showing that the combination
of genes underlying addiction disorders was also associated with
regulation of dopamine signaling.


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FULL STORY ==========================================================================
By combing through genomic data of over 1 million people, scientists have identified genes commonly inherited across addiction disorders, regardless
of the substance being used. This dataset -- one of the largest of its
kind -- may help reveal new treatment targets across multiple substance
use disorders, including for people diagnosed with more than one. The
findings also reinforce the role of the dopamine system in addiction,
by showing that the combination of genes underlying addiction disorders
was also associated with regulation of dopamine signaling.


========================================================================== Published today in Nature Mental Health, the study was led by researchers
at the Washington University in St. Louis, along with more than 150
coauthors 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),
the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute on Aging.

There has been limited knowledge of the molecular genetic underpinnings of addiction until now. Further, most clinical trials and behavioral studies
have focused on individual substances, rather than addiction more broadly.

Genetics play a key role in determining health throughout our lives,
but they 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," 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." In 2021, more than 46 million people in the United
States aged 12 or older had at least one substance use disorder, and
only 6.3% had received treatment.

Moreover, people who use drugs are facing an increasingly dangerous
drug supply, now often tainted with fentanyl. Approximately 107,000
people died of drug overdoses in 2021, and 37% of these deaths involved simultaneous exposure to both opioids and stimulant drugs. Drug use and addiction represent a public health crisis, characterized by high social, emotional, and financial costs to families, communities, and society.

Substance use disorders are heritable and influenced by complex
interactions among 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 certain disorders. This
method involves searching entire genomes for regions of genetic variation, called single-nucleotide polymorphisms (SNPs), that associate with the
same disease, disorder, condition, or behavior among multiple people.

In this study, researchers used this method to pinpoint areas in the
genome associated with general addiction risk, as well as the risk of
specific substance use disorders -- namely, alcohol, nicotine, cannabis,
and opioid use disorders -- in a sample of 1,025,550 individuals with
genes indicating European ancestry and 92,630 individuals with genes
indicating African ancestry.

"Using genomics, we can create a data-driven pipeline to prioritize
existing medications for further study and improve chances of discovering
new treatments. To do this accurately, it's critical that the genetic
evidence we gather includes globally representative populations and
that we have members of communities historically underrepresented in
biomedical research leading and contributing to these kinds of studies,"
said Alexander Hatoum, Ph.D., a research assistant professor at Washington University in St. Louis and lead author of the study.

Hatoum and the research team discovered various molecular patterns
underlying addiction, including 19 independent SNPs significantly
associated with general addiction risk and 47 SNPs for specific substance disorders among the European ancestry sample. 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.

Compared to other genetic predictors, the genomic pattern identified here
was also a more sensitive predictor of having two or more substance
use disorders at once. The genomic pattern also predicted higher
risk of mental and physical illness, including psychiatric disorders,
suicidal behavior, respiratory disease, heart disease, and chronic pain conditions. In children aged 9 or 10 years without any experience of
substance use, these genes correlated with parental substance use and externalizing behavior.

"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.

The shared genetic mechanisms between substance use and mental disorders revealed in this study underscore the importance of thinking about these disorders in tandem," said NIMH Director Joshua A. Gordon, M.D., Ph.D.

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

The inclusion of data from different ancestral groups in this study cannot
and should not be used to assign or categorize variable genetic risk for substance use disorder to specific populations. As genetic information
is used to better understand human health and health inequities,
expansive and inclusive data collection is essential. NIDA and other
Institutes at NIH supported a recently released report on responsible
use and interpretation of population-level genomic data by the National Academies of Sciences, Engineering, and Medicine.

While Hatoum and colleagues have identified a genetic pattern indicating
broad addiction risk, they note that substance use-specific diagnoses
still have meaning. "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 NIAAA Director
George F. Koob, Ph.D. "The finding of shared genetic risk variants
across different 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 powerful
support for individualized prevention and treatment." This study was
supported by multiple grants: NIDA (T32DA007261, DA054869, R01DA054750, K02DA032573, U01DA055367, K01DA051759, DP1DA054394, R33DA047527); NIAAA (K01AA030083, R21AA027827, R01AA027522, F31AA029934, T32AA028259); NIMH (K23MH121792, T32MH014276, R01MH120219); NIA (RF1AG073593, P30AG066614);
NICHD (P2CHD042849)
* RELATED_TOPICS
o Health_&_Medicine
# Personalized_Medicine # Controlled_Substances #
Diseases_and_Conditions # Mental_Health_Research
o Mind_&_Brain
# Addiction # Illegal_Drugs # Disorders_and_Syndromes #
Mental_Health
* RELATED_TERMS
o Addiction o Drug_addiction o Alcoholism o Dopamine o
Sleep_disorder o Mental_illness o Personality_disorder o
Dopamine_hypothesis_of_schizophrenia

========================================================================== Story Source: Materials provided by
NIH/National_Institute_on_Drug_Abuse. Note: Content may be edited for
style and length.


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10.1038/s44220- 023-00034-y ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/03/230322140341.htm

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