Gene-environment interplay underlying negative family environments and family-based interventions in early adolescent substance use

负面家庭环境和青少年早期药物使用的家庭干预背后的基因-环境相互作用

• 批准号: 9384460
• 负责人: Kit Elam
• 金额: $ 13.28万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9384460
• 关键词: 13 year old; 3 year old; Address; Adolescence; Adolescent; Age; Alcohol or Other Drugs use; Arizona; Bioinformatics; Biological; Buffers; Child; Child Rearing; Collaborations; Complement; Data; Development; Disinhibition; Educational workshop; Environment; Esthesia; Etiology; Family; Family dynamics; Federal Government; Genes; Genetic; Genetic Markers; Genetic Predisposition to Disease; Genomics; Goals; Grant; Impulsivity; Individual Differences; Institutes; Instruction; Intervention; Local Government; Longitudinal Studies; Measures; Mediation; Mentors; Mentorship; Meta-Analysis; Methods; Mission; National Institute of Drug Abuse; Outcome; Pathway Analysis; Pathway interactions; Prevention; Preventive Intervention; Public Health; Randomized; Reading; Recruitment Activity; Research; Research Personnel; Risk; Role; Sampling; Schools; Single Nucleotide Polymorphism; State Government; Strategic Planning; Substance Addiction; Supervision; Teenagers; Testing; Training; Training Programs; Treatment Efficacy; United States National Institutes of Health; Universities; Writing; addiction; adolescent substance use; base; career; checkup examination; cost; critical period; early adolescence; emerging adulthood; experience; family influence; gene environment interaction; genome wide association study; high risk; improved; innovation; interest; intervention effect; intervention program; next generation; novel; responsible research conduct; social

PROJECT SUMMARY This K01 will provide the applicant with training in support of becoming an independent, interdisciplinary researcher on the interplay among children’s biologically-informed genetic predispositions for behavioral disinhibition (impulsivity, sensation seeking, externalizing), negative family environments, and family-based prevention effects in pathways to early adolescent substance use. The applicant will accomplish this objective through (1) developing expertise in advanced genomic (e.g., genome-wide associations and meta-analysis) and bioinformatics methods (e.g., functional annotation, pathway and gene-network analyses) to create biologically-informed markers of genetic predisposition; and (2) gaining an interdisciplinary understanding of adolescent substance use across genetic, familial, and prevention domains. These goals will be accomplished through genomics and bioinformatics workshops, formal coursework in bioinformatics and substance use, and mentored instruction (including directed readings and supervised research experiences). Instruction will be complemented by professional development seminars, grant writing workshops, and training in the responsible conduct of research. Training will be accomplished at Arizona State University’s (ASU’s) School of Social and Family Dynamics and REACH Institute, with primary mentorship from Dr. Thomas Dishion (expert in family- based prevention of adolescent substance use). Co-mentorship will be provided by Dr. Laurie Chassin (expert in substance use etiology), Dr. Kathryn Lemery-Chalfant (expert in gene-environment interplay), and Dr. Valentin Dinu (expert in bioinformatics and genomics), and collaboration with Dr. Arpana Agrawal (expert in advanced genetic methods in substance use) and Dr. David MacKinnon (expert in causal mediation analyses). The first aim is to examine if biologically-informed genetic predispositions for behavioral disinhibition evoke and/or moderate negative family environments in predicting early adolescent substance use. It is hypothesized that genetic predisposition will be moderated by and evoke negative family environments, which will contribute to early adolescent substance use. The second aim is to examine if family-based prevention effects moderate genetic predispositions for behavioral disinhibition—or moderate genetically evoked negative family environments—in predicting early adolescent substance use. It is hypothesized that genetic predisposition will be moderated by prevention effects in predicting early adolescent substance use and that prevention effects will buffer the genetic evocation of negative family environments. Aims will be tested in the Early Steps (age 2– 15.5) and Project Alliance 1 (age 11–27) samples, which are large, genetically-sensitive longitudinal studies of familial and family-based prevention effects on adolescent substance use. Training in bioinformatics methods will be used to refine and create measures of biologically-informed genetic predisposition to examine gene- environment interplay. These training and research objectives address NIDA’s strategic plan to investigate gene-environment interplay in adolescent substance use and inform next generation interventions.

项目概要 该 K01 将为申请人提供培训，以支持其成为独立的、跨学科的 研究人员研究儿童行为遗传倾向之间的相互作用 去抑制（冲动、寻求感觉、外化）、消极的家庭环境和以家庭为基础的 申请人将实现这一目标。 通过（1）发展高级基因组方面的专业知识（例如全基因组关联和荟萃分析） 和生物信息学方法（例如功能注释、通路和基因网络分析）来创建 遗传易感性的生物学标记；(2) 获得跨学科的理解 这些目标将在遗传、家族和预防领域实现。 通过基因组学和生物信息学研讨会、生物信息学和物质使用的正式课程，以及 指导性指导（包括指导性阅读和指导性研究经验）。 辅之以专业发展研讨会、拨款写作研讨会和负责人培训 研究的进行将在亚利桑那州立大学 (ASU) 社会与学院完成。 家庭动力和 REACH 研究所，主要由 Thomas Dishion 博士（家庭专家）指导 Laurie Chassin 博士（专家）将提供共同指导。 物质使用病因学博士），Kathryn Lemery-Chalfant 博士（基因与环境相互作用专家）和 Valentin Dinu（生物信息学和基因组学专家），以及与 Arpana Agrawal 博士（生物信息学和基因组学专家）的合作 物质使用方面的先进遗传方法）和 David MacKinnon 博士（因果中介分析专家）。 第一个目的是检查行为去抑制的生物学信息遗传倾向是否会引起 和/或中度负面家庭环境可预测青少年早期物质使用。 遗传倾向将受到负面家庭环境的调节并引发负面家庭环境，这将有助于 第二个目的是检查以家庭为基础的预防效果是否适度。 行为去抑制的遗传倾向——或中度遗传诱发的负面家庭 环境——在预测青少年早期物质使用方面开创了先河。 可以通过预测青少年早期物质使用的预防效果来调节，并且预防效果 将缓冲负面家庭环境的基因诱发 目标将在早期阶段（2-3 岁）进行测试。 15.5）和项目联盟1（11-27岁）样本，这是大型的、遗传敏感的纵向研究 家庭和基于家庭的预防对青少年药物使用的影响。生物信息学方法培训。 将用于完善和创建生物学信息遗传易感性的测量方法，以检查基因 这些培训和研究目标涉及 NIDA 的调查战略计划。 基因与环境在青少年物质使用中的相互作用，并为下一代干预措施提供信息。