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

项目总结/摘要 近几十年来，大麻在娱乐用途和合法化方面普遍增加。 吸食大麻，特别是在青少年时期开始吸食大麻，与多个领域的损害有关 认知和心理健康。最近，基因研究发现了几种与大麻有关的变异 使用和大麻使用障碍，以及与大麻遗传相关的几种表型 使用.然而，目前还不清楚大麻使用的遗传风险如何影响青少年的发育和行为， 特别是在开始使用药物之前。 在这个项目中，我计划使用先进的统计建模方法来研究几个因素的影响。 物质使用行为遗传风险特征。该项目的目标1将测试大麻使用的影响 疾病遗传风险评分，以及已知与大麻使用有关的几种遗传风险评分， 在两个大样本的物质幼稚青少年的心理健康和行为的多个领域（ 青少年大脑和认知发展研究[ABCD]，以及挪威母亲，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评分纳入 单变量和多变量统计模型，这个项目将能够梳理除了独特的和重叠的 与其他遗传风险特征相比，大麻使用障碍遗传风险的影响。目标2将遵循 类似的分析技术，应用于大脑中的限制光谱成像测量，以了解 大麻使用的遗传风险对青少年大脑微结构的影响 ABCD研究。最后，目标3将纳入大麻使用的遗传风险、儿童心理健康措施， 和大脑微结构来预测经常使用大麻的年龄。根据该组织的动机， ABCD研究，该项目将使用暴露前的数据，以帮助预测物质使用行为， 青春期 拟议的研究项目将利用现有的基于人口的纵向数据集， 遗传变异、大脑发育和行为之间的相互作用。添加几个相关的基因 我们的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，对发展开始之前和之后的审查， 大麻使用将有助于了解大麻使用与发展之间的关系， 并将使我们能够区分大麻使用后的影响和那些可能导致 青少年开始开始使用。

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.