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

项目摘要 本行政补编是针对NOT-DA-24-003快速翻译物质用途而提交的 以及成瘾流行病学和预防干预研究，建议将研究结果转化为 从父项目R01DA050721中脱颖而出，使用物质使用障碍的遗传结构来 《先进的基因鉴定和风险途径的理解》来研究我们的基因的应用 流行病学发现作为一种新的预防干预措施，以减少危险的物质使用模式 新兴的成年人。母项目有两个相辅相成的目标：(1)推进相关基因的发现 使用新的多变量基因组技术在物质使用障碍中，以及(2)表征风险 在不同的纵向样本中与识别的变体相关联，跨开发，并与 环境。自从亲本启动以来，我们在基因鉴定方面取得了巨大的进步 R01，我们最新的全基因组关联研究的结果解释了大约10%的变异 在独立样本中的物质使用和相关结果。我们已经整合了由此产生的多基因 具有行为和环境风险因素的流行病学信息的得分，使用来自多个 不同的纵向队列，以创建个人风险估计，发现流行病学的组合 风险信息和遗传数据有助于预测谁有更高的药物使用风险 初露头角的成年期障碍。这项工作的基本原理是，它将为 个性化医疗，提供个性化风险信息，帮助预防 问题和/或允许更早的干预。利用这项补充的行政拨款，我们建议： (目标1)创建一个新的预防/干预方案，包括一个在线平台，供个人 接收他们对成瘾风险的个性化风险估计，通过整合关于他们的 遗传、行为和环境风险因素基于父母资助的研究，其次是 有关如何降低风险的信息，随着具有以下专业知识的新合作者的加入而开发 行为改变；和(目标2)对新加入的成年人(18-25岁)进行小型随机对照试验(N=400) 危险物质使用和问题发展的高风险期，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研究成果转化为预防干预措施的关键第一步。

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.