Predicting Genetic Risk for Impulsivity and Substance Use in Adolescence

Area of Science:

• Behavioral Genetics
• Adolescent Development
• Substance Use Research

Background:

• Understanding genetic factors in adolescent substance initiation is key for early identification and prevention.
• Adolescence is a critical period for brain development and the onset of substance experimentation.

Purpose of the Study:

• To assess polygenic scores (PGSs) for predicting impulsivity and self-reported substance use in early-to-mid adolescence.
• To examine how these genetic associations change across different age bands (9-15 years) and ancestral groups.

Main Methods:

• Utilized polygenic scores (PGSs) from the PGS catalog for substance use-related traits.
• Analyzed data from the Adolescent Brain Cognitive Development (ABCD) Study (N=8,753) across age bands (9-10, 11-13, 13-15).
• Conducted ancestry-stratified analyses (European-like, African-like, Mixed-like) due to known ancestry biases in genetic discovery samples.

Main Results:

• In European-like individuals, nicotine/tobacco PGSs correlated with higher impulsivity across all UPPS-P subscales and ages.
• Associations between PGSs and impulsivity varied with age, with some increasing and others decreasing over time.
• Nicotine/tobacco PGSs predicted caffeine consumption, and at ages 13-15, predicted cannabis and tobacco use.
• Energy drink consumption associations with nicotine/tobacco and alcohol PGSs increased with age.
• Replication in African-like and Mixed-like groups showed attenuated effects, emphasizing the need for diverse genetic cohorts.

Conclusions:

• Genetic predisposition, impulsivity, and substance initiation show dynamic interplay throughout adolescence.
• Caffeine consumption may serve as an early risk factor for later problematic substance use.
• Polygenic scores, combined with comprehensive phenotypic data, can aid in identifying individuals for targeted prevention efforts.
• Ancestral diversity in genetic studies is crucial for robust and generalizable findings.