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

在两个大型纵向青少年队列中，遗传对行为、大脑发育和物质使用的影响

• 批准号: 10679774
• 负责人: Diana Mun Yee Smith
• 金额: $ 4.02万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10679774
• 关键词: Adolescence; Adolescent; Adolescent Behavior; Adolescent Development; Affect; Age; Age of Onset; Behavior; Behavioral; Behavioral Symptoms; Bipolar Disorder; Birth; Brain; Brain imaging; Cannabis; Child; Childhood; Cognition; Cognitive; Cohort Studies; Complex; Data; Data Set; Development; Diffusion Magnetic Resonance Imaging; Doctor of Philosophy; Fathers; Genetic; Genetic Predisposition to Disease; Genetic Risk; Genetic Variation; Genetic study; Impairment; Individual; Investigation; Label; Legal; Measures; Mental Health; Methods; Modeling; Mothers; Motivation; Onset of illness; Other Genetics; Participant; Patient Self-Report; Patients; Phenotype; Population; Positioning Attribute; Prevalence; Problem behavior; Process; Psychoses; Public Health; Public Policy; Recreation; Recreational Drugs; Reporting; Research; Research Project Grants; Restriction Spectrum Imaging; Rewards; Role; Sampling; Sampling Studies; Statistical Models; Structure; Techniques; Testing; Time; United States; Variant; Work; cannabis use behavior; cognitive development; cohort; density; early onset; genetic variant; genomic locus; gray matter; hazard; improved; longitudinal dataset; marijuana legalization; marijuana use; marijuana use disorder; multimodality; neuroimaging; polygenic risk score; population based; predictive modeling; psychogenetics; substance use; white matter

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.

项目摘要/摘要 近几十年来，大麻在娱乐使用和合法化方面经历了宽度的增加。 大麻使用，尤其是在青春期开始时，它与多个领域的损害有关 认知和心理健康。最近，遗传研究发现了与大麻相关的几种变体 使用和大麻使用障碍，以及几种与大麻相关的表型 使用。但是，目前尚不清楚使用大麻的遗传风险如何影响青少年的发展和行为， 特别是在使用物质使用之前的时期。 在这个项目中，我计划在统计建模中使用高级方法来检查几种的影响 物质在行为上使用遗传风险特征。该项目的目标1将测试大麻使用的影响 遗传风险评分以及已知与大麻使用相关的几种遗传风险评分 在两个不含物质的青少年的大型样本中，心理健康和行为的多个领域（ 青春期的大脑和认知发展研究[ABCD]，挪威母亲，父亲和孩子 队列研究[MOBA]）总计超过115,000名参与者。通过将多个相关的遗传风险得分纳入 单变量和多元统计模型，该项目将能够教授独特而重叠的 与其他遗传风险谱相比，遗传风险对大麻使用障碍的影响。 AIM 2将遵循 类似的分析技术，应用于大脑中的限制频谱成像度量，以了解 遗传风险使用大麻对从未从事大麻对大脑微观结构的影响。 ABCD研究。最后，AIM 3将纳入使用大麻的遗传风险，儿童心理健康措施， 和脑微观结构，以预测常规大麻使用的开始年龄。符合动力 ABCD研究，该项目将使用暴露前数据来帮助预测物质使用行为 青少年。 拟议的研究项目将利用现有的基于人群的纵向数据集嘲笑 遗传变异，大脑发育和行为之间的相互作用。增加了几个相关遗传 统计模型的风险评分将使我们能够了解有助于 大脑结构和行为。重要的是，倡议之前和之后的发展检查 大麻使用将有助于理解大麻使用和开发之间的关系， 并将允许我们区分随后的大麻使用效果与可能易感的效果 青少年开始使用。