Using the Genetic Architecture of Substance Use Disorders to Advance Gene Identification and Understanding of Pathways of Risk

项目摘要 本行政补充文件是根据NOT-DA-24-003《物质使用快速翻译》提交的 和成瘾流行病学和预防干预研究，建议将研究结果 来自母项目R 01 DA 050721“利用物质使用障碍的遗传结构， 推进基因识别和风险途径的理解”，以研究我们的基因的应用， 流行病学调查结果作为一种新的预防干预措施，以减少 新兴的成年人。母项目有两个互补的目标：（1）推进相关基因的发现 使用新的多元基因组学技术在物质使用障碍中，以及（2）表征风险 与不同纵向样本中确定的变异相关，跨越发展，并与 环境保护自从父母开始，我们在基因鉴定方面取得了巨大的进步 R 01，我们最近的全基因组关联研究的结果占方差的10%左右 药物使用和相关结果的独立样本。我们整合了多基因 使用来自多个国家和地区的数据， 不同的纵向队列，以建立个人风险估计，发现流行病学的组合， 风险信息和遗传数据有意义地有助于预测谁处于物质使用的高风险中 成年期出现的障碍这项工作的基本原理是，它将奠定基础， 个性化医疗，提供个性化的风险信息，帮助预防 问题和/或允许早期干预。利用这笔补助金的行政经费，我们建议 (Aim 1）建立一个新的预防/干预方案，包括一个供个人使用的在线平台， 接收他们的成瘾风险的个性化风险估计，通过整合他们的个人信息， 遗传，行为和环境风险因素的基础上，研究从父母补助金，其次是 关于如何降低风险的信息，增加了具有以下专业知识的新合作者 行为改变;和（目标2）对正在进入研究的新兴成年人（18- 25岁）进行一项小型RCT（N=400） 危险物质使用升级的高风险期和问题的发展，以测试是否 个性化反馈计划的完成与危险物质使用的减少有关。这 该项目是将遗传流行病学调查结果转化为预防干预措施的关键的第一步。

Project Summary This administrative supplement, submitted in response to NOT-DA-24-003 Rapid Translation of Substance Use and Addiction Epidemiology and Prevention Intervention Research, proposes to translate the findings emerging from the parent project R01DA050721 “Using the genetic architecture of substance use disorders to advance gene identification and understanding of pathways of risk” to study the application of our genetic epidemiological findings as a novel prevention intervention to reduce risky patterns of substance use among emerging adults. The parent project has two complementary goals: (1) to advance discovery of genes involved in substance use disorders using new multivariate genomic techniques, and (2) to characterize the risk associated with identified variants in diverse longitudinal samples, across development, and in conjunction with the environment. We have made tremendous advances in gene identification since the initiation of the parent R01, with the results from our most recent genome-wide association study accounting for ~10% of the variance in substance use and related outcomes in independent samples. We have integrated the resulting polygenic scores with epidemiological information on behavioral and environmental risk factors, using data from multiple diverse longitudinal cohorts, to create individual risk estimates, finding that the combination of epidemiological risk information and genetic data meaningfully contribute to predicting who is at elevated risk of substance use disorders in emerging adulthood. The rationale for this line of work is that it will lay the foundation for personalized medicine, with the provision of personalized risk information helping prevent the development of problems and/or allow for earlier intervention. With administrative funds from this supplement, we propose to (Aim 1) create a new prevention/intervention program, consisting of an on-line platform for individuals to receive their personalized risk estimates for addiction risk, generated by integrating information about their genetic, behavioral, and environmental risk factors based on research from the parent grant, followed by information about how to reduce risk, developed with the addition of new collaborators with expertise in behavior change; and (Aim 2) conduct a small RCT (N=400) with emerging adults (18-25yrs), who are entering the high-risk period for escalation of risky substance use and the development of problems, to test whether completion of the personalized feedback program is associated with reductions in risky substance use. This project represents a critical first step in translating genetic epidemiological findings to prevention intervention.