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

数据驱动的暴露体对青春期饮酒影响的探索

• 批准号: 10826809
• 负责人: Faith Adams
• 金额: $ 4.61万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-11 至 2025-09-10
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10826809
• 关键词: 10 year old; 15 year old; Address; Adolescence; Adolescent; Affect; Age; Alcohol consumption; Alcoholism; Anterior; Behavioral; Benchmarking; Big Data; Bioinformatics; Brain; Child Abuse and Neglect; Clinical; Cohort Studies; Complex; Data; Data Reporting; Data Science; Decision Making; Development; Diabetes Mellitus; Diet; Dimensions; Environment; Environmental Exposure; Environmental Risk Factor; Equity; Etiology; European; European ancestry; Exclusion; Family; Family history of; Functional Magnetic Resonance Imaging; Future; Genetic; Genetic study; Genome; Goals; High Performance Computing; Home; Individual; Inferior frontal gyrus; Institution; Instruction; Intervention; Life Style; Link; Mediating; Medical; Mentors; Mission; National Institute on Alcohol Abuse and Alcoholism; Neighborhoods; Neurobiology; Outcome; Participant; Patient Self-Report; Performance; Play; Policies; Pollution; Population; Poverty; Predisposition; Prefrontal Cortex; Prevalence; Prevention; Public Health; Reaction Time; Research; Resources; Risk; Risk Factors; Role; Sampling; Schools; Shapes; Siblings; Signal Transduction; Social Desirability; Techniques; Training; Training Programs; Youth; addiction; alcohol behavior; alcohol misuse; alcohol outlet density; alcohol risk; alcohol use disorder; alcohol use initiation; big-data science; binge drinking; biopsychosocial factor; career; cingulate cortex; clinical application; clinically actionable; cognitive development; cohort; computer science; density; distilled alcoholic beverage; drinking; early alcohol use; effective intervention; ethnoracial; experience; genetic risk factor; genetic variant; genome wide association study; insight; medical schools; motor control; neural; neurobehavioral; neuroimaging; non-genetic; novel; parental monitoring; peer; polygenic risk score; prevent; prospective; racial bias; response; risk mitigation; skills; social; social stigma; socioeconomics; substance use; underage drinking; young adult

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.

项目摘要/摘要 美国的未成年人饮酒是一个严重的公共卫生问题。早期饮酒（<15岁）， 与以后开始饮酒的人相比，患饮酒障碍的风险增加了七倍。 因此，对与早期酒精使用相关的生物心理社会因素的全面理解 在青春期，对于解决这个问题至关重要。为此，已经进行了广泛的研究，并 确定了与未来饮酒有关的遗传因素，例如酒精中毒家族史和较高的多基因 责任。有限的遗传研究范围提出了重大挑战，包括（1）主要包含 欧洲血统的参与者，（2）在酒精使用早期阶段排除那些人，以及（3）不清楚 临床适用性。这需要探索非遗传环境暴露（即 与酒精使用起来相关的exposome）。因此，拟议的研究旨在利用高度的数据 青少年的大脑认知发展研究（ABCD; n = 11,000， 9-10岁），并使用新型的全外展览会研究（XWAS）进行识别 外卵形危险因素并得出多曝光酒精风险评分（PXARS），用于酒精使用。 远至14岁的青少年。PXAR的表现将针对这些已建立的遗传进行基准测试 风险因素。此外，饮酒的风险与抑制性较差有关。因此，这提出了 项目将全面检查前瞻性饮酒的神经生物学和行为相关性 使用来自停止信号任务（SST）的数据发作。研究还表明，爆炸因素可能会影响 抑制控制发展；因此，本研究旨在发现神经行为之间的关联 因素，PXAR和酒精使用。与研究基因组不同，检查杂物体允许 调查环境的整体（即自然，建造和社交），以发现潜在的临床 可操作的目标。虽然许多外卵形预测因子可能不容易修改（例如，种族偏见，， 社会经济障碍），但仍然需要仔细检查；其他预测因素（例如，同龄人，饮食和活动）可能 可行的预防和干预目标，以防止和最大程度地减少青年饮酒。提议 研究为申请人提供了一个强大而全面的培训计划，其中包括深入的教学 大数据和生物信息学方法以及基于任务的fMRI技术，将显着加强 申请人的技能。申请人将获得高技能赞助商团队的杰出支持， 在物质使用神经生物学，外博学和 神经影像学。此外，该研究将在伊坎医学院进行，这是一个享誉世界的 提供顶级培训，课程和机构资源的机构，包括但不限于 成瘾研究所，外博研究所和高性能计算核心 执行拟议的研究的理想设置。