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Youth Correlates of Genetic Liability to Substance Use Disorders
Sarah E Paul1, Aaron J Gorelik1, Nicole R Karcher2
1Psychological & Brain Sciences, Washington University in Saint Louis, Saint Louis, Missouri.
Medrxiv : the Preprint Server for Health Sciences
|December 8, 2025
Summary
Genetic predisposition to substance use disorders (SUDs) appears in childhood, not just adolescence. Early identification of these risk factors, like mental health and sleep issues, may help prevent future addiction.
Area of Science:
- Genetics
- Neuroscience
- Developmental Psychology
Background:
- Substance use disorders (SUDs) are heritable and emerge during adolescence/young adulthood.
- The origins of SUD correlations (predisposition vs. consequence) are not fully understood.
Purpose of the Study:
- To investigate the early genetic underpinnings of SUDs in children.
- To identify phenotypic associations related to SUD polygenic risk scores (PRS) in pre-adolescents.
Main Methods:
- Conducted a phenome-wide association study (PheWAS) using data from the Adolescent Brain Cognitive Development (ABCD) Study.
- Analyzed polygenic risk scores for various SUDs (Problematic Alcohol Use, Tobacco Use Disorder, Cannabis Use Disorder, Opioid Use Disorder, Addiction Risk Factor).
- Examined associations with mental health, sleep, screen time, and caffeine consumption phenotypes.
Main Results:
- Identified 309 phenotypic associations with SUD PRS in 8-13-year-old children.
- Most associations were found in participants not yet exposed to substances.
- Neuroimaging data partially explained links between SUD PRS and screen time.
Conclusions:
- Genetic liability for SUDs manifests in childhood as potentially modifiable risk factors.
- Early identification and intervention targeting these childhood phenotypes could mitigate later SUD development.
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