An Initial Genetic Correlation Analysis of Externalizing Behavior and Neuroimaging Phenotypes in the ABCD Cohort

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Adolescent externalizing behaviors are significant risk factors for future substance use and psychiatric disorders.
• Understanding the genetic basis of these behaviors and their relationship with brain imaging phenotypes is crucial for youth cohorts.
• Scalable genome-wide methods are needed to analyze large youth datasets.

Purpose of the Study:

• To implement a genome-wide association study (GWAS) pipeline for longitudinal externalizing traits and brain imaging phenotypes in adolescents.
• To investigate the genome-wide genetic correlations between regional cortical morphology and externalizing phenotypes.
• To assess the feasibility of using large-scale youth data for imaging-genetics research.

Main Methods:

• Utilized data from the Adolescent Brain Cognitive Development (ABCD) Study^®.
• Performed quality-controlled genotype processing and harmonized phenotype datasets.
• Conducted GWAS using REGENIE and estimated genetic correlations with cross-trait LD Score Regression (LDSC).

Main Results:

• Analyzed three externalizing phenotypes and approximately 200 imaging-derived phenotypes (IDPs).
• Exploratory analysis revealed nominal statistical significance for some associations, but none survived multiple comparison correction.
• Genetic correlation estimates were limited by sample size, heritability uncertainty, and the number of comparisons.

Conclusions:

• The study did not find significant evidence for shared genetic architecture between adolescent externalizing behaviors and cortical morphology.
• The lack of significant findings may be attributed to limitations in current imaging GWAS sample sizes and statistical power.
• Larger imaging-genetics cohorts and replication studies are necessary to detect potential modest or specific genetic correlations.