# Genetic influence on behavior, brain development, and substance use in two large, longitudinal adolescent cohorts

> **NIH NIH F30** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $40,248

## Abstract

PROJECT SUMMARY/ABSTRACT
Cannabis has undergone widespread increases in recreational use and legalization in recent decades.
Cannabis use, particularly when it begins in adolescence, is associated with impairments in multiple domains
of cognition and mental health. Recently, genetic studies have found several variants associated with cannabis
use and cannabis use disorder, as well as several phenotypes that are genetically correlated with cannabis
use. However, it is unclear how genetic risk for cannabis use affects adolescent development and behavior,
particularly in the period before substance use begins.
In this project I plan to use advanced methods in statistical modeling to examine the effects of several
substance use genetic risk profiles on behavior. Aim 1 of this project will test the influence of a cannabis use
disorder genetic risk score, as well as several genetic risk scores known to be related to cannabis use, on
multiple domains of mental health and behavior in two large samples of substance-naïve adolescents (The
Adolescent Brain and Cognitive Development Study [ABCD], and the Norwegian Mother, Father and Child
Cohort Study [MoBa]) totaling over 115,000 participants. By incorporating multiple related genetic risk scores in
univariate and multivariate statistical models, this project will be able to tease apart the unique and overlapping
effects of genetic risk for cannabis use disorder compared to other genetic risk profiles. Aim 2 will follow a
similar analysis technique, applied to restriction spectrum imaging measures in the brain, to understand the
influence of genetic risk for cannabis use on brain microstructure in substance-naïve adolescents from the
ABCD study. Finally, Aim 3 will incorporate genetic risk for cannabis use, childhood mental health measures,
and brain microstructure to predict age of onset of regular cannabis use. In line with the motivation of the
ABCD Study, this project will use pre-exposure data to aid in prediction of substance use behavior during
adolescence.
The proposed research project will leverage existing population-based longitudinal datasets to tease apart the
interplay between genetic variation, brain development, and behavior. The addition of several related genetic
risk scores to our statistical models will allow us to understand the shared genetic variants that contribute to
brain structure and behavior. Importantly, the examination of development both before and after the initiation of
cannabis use will be instrumental in understanding the relationship between cannabis use and development,
and will allow us to distinguish effects that follow from cannabis use versus those that may predispose
adolescents to begin using.

## Key facts

- **NIH application ID:** 10679774
- **Project number:** 1F30DA057078-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Diana Mun Yee Smith
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $40,248
- **Award type:** 1
- **Project period:** 2023-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10679774

## Citation

> US National Institutes of Health, RePORTER application 10679774, Genetic influence on behavior, brain development, and substance use in two large, longitudinal adolescent cohorts (1F30DA057078-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10679774. Licensed CC0.

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