A Decade of Discovery: Leveraging Genomic Data in the ABCD Study to Illuminate Adolescent Neurodevelopment

The Adolescent Brain Cognitive Development (ABCD) Study provides an unprecedented resource for developmental genomics, offering genetic data for more than 11,000 youth, as well as extensive longitudinal behavioral, neuroimaging, environmental, and real-world digital phenotyping measures. In this review, we summarize the scope and utility of the ABCD genetics data and provide a review of ABCD genetics publications over the past decade. We first describe the genetic data available through the consortium, including pipelines used for genotyping, imputation, and ancestry information, and review commonly used methods for admixture estimation, relatedness, genome-wide association studies, and polygenic score analyses. Key methodological considerations are highlighted to guide analyses, with an emphasis on addressing population structure to promote reproducibility and ensure validity across diverse populations. We then synthesize findings from the first decade of ABCD research leveraging measured genetic data, highlighting progress in several key domains: neurodevelopment, substance use, cognition, sleep, impulsivity and externalizing behaviors, and psychosis. Finally, we discuss key challenges and opportunities including the need for robust analytic strategies to maximize use of admixed and cross-ancestry genetic data to ensure that findings are generalizable to the diverse ancestral distribution of the U.S. population, application of advanced statistical methods to model gene x environment interactions, and the use of real-world digital phenotyping data. Together, these efforts will enhance the translational relevance of ABCD genetics data, enabling identification of genetic and environmental factors that shape adolescent neurodevelopment, long-term health, and wellbeing. • The ABCD Study provides genotyping data for over 11,000 youth. • Important analytical considerations include handling of admixture and relatedness. • SNP-based effects are modest and interact with the environment to shape outcomes. • Association studies show polygenic liability has broad cross-trait effects.