Data-Driven Exploration of Exposomic Influences on the Onset of Alcohol Use During Adolescence

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Project Summary/Abstract Underage drinking in the US is a serious public health concern. Early onset of alcohol use (<15 years old), increases the risk of developing alcohol use disorder by seven times compared to those who start drinking later. Therefore, a comprehensive understanding of biopsychosocial factors associated with early alcohol use onset in adolescence is crucial to address this problem. To this end, extensive studies have been conducted and have identified genetic factors linked to future alcohol use, such as family history of alcoholism and higher polygenic liability. The limited scope of genetic studies poses significant challenges including the (1) primary inclusion of participants of European ancestry, (2) exclusion of those in the early stages of alcohol use, and (3) unclear clinical applicability. This necessitates the need for exploring non-genetic environmental exposures (i.e., exposome) associated with alcohol use onset. As such, the proposed study aims to leverage data from the highly powered and nationally diverse cohort, the Adolescent Brain Cognitive Development Study (ABCD; n = 11,000, 9-10-year-olds), and use a novel eXposome-Wide Association Studies (XWAS) approach to identify exposomic risk factors and derive PolyeXposure Alcohol Risk Scores (PXARS) for alcohol use onset in adolescents up to age 14. The performance of PXARS will be benchmarked against these established genetic risk factors. Furthermore, the risk for alcohol use onset is linked to poor inhibitory control; thus, this proposed project will comprehensively examine the neurobiological and behavioral correlates of prospective alcohol use onset using data from the Stop Signal Task (SST). Studies also suggest that exposomic factors may influence inhibitory control development; therefore, this study aims to uncover associations between neurobehavioral factors, PXARS, and alcohol use onset. Unlike studying the genome, examining the exposome allows for investigating the totality of the environment (i.e., natural, built, and social) to uncover potentially clinically actionable targets. While many exposomic predictors may not be easily modifiable (e.g., racial biases, socioeconomic barriers) but still warrant close examination; other predictors (e.g., peers, diet, and activities) may be viable prevention and intervention targets for preventing and minimizing alcohol use in youth. The proposed study offers the applicant a robust and comprehensive training program, which includes in-depth instruction on big data and bioinformatics approaches, as well as task-based fMRI techniques and will significantly strengthen the applicant's skillset. The applicant will receive exceptional support from a team of highly skilled sponsors and consultants who have extensive experience in the fields of substance use neurobiology, exposomics, and neuroimaging. Furthermore, the research will be conducted at the Icahn School of Medicine, a world-renowned institution that offers top-tier training, coursework, and institutional resources including but not limited to the Addiction Institute, the Institute for Exposomic Research, and the High-Performance Computing Core, making it an ideal setting for executing the proposed study.