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

利用药物滥用疾病的遗传结构来推进基因识别和对风险途径的理解

• 批准号: 10765309
• 负责人: DANIELLE M DICK
• 金额: $ 24.08万
• 依托单位: RUTGERS BIOMEDICAL AND HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10765309
• 关键词: Accounting; Administrative Supplement; Applied Genetics; Area; Behavioral; Communities; Coupled; Data; Development; Disease; Early Intervention; Enrollment; Environment; Environmental Risk Factor; Epidemiology; Feedback; Foundations; Funding; Genes; Genetic; Genome; Genomics; Goals; Growth; Individual; Intervention; Intervention Studies; Knowledge; Literature; Longitudinal cohort; Methods; Modeling; Outcome; Parents; Pathway interactions; Pattern; Phenotype; Play; Prevention; Research; Risk; Risk Estimate; Risk Reduction; Role; Sampling; Substance Addiction; Substance Use Disorder; Sum; Techniques; Testing; Time; Translating; Translations; Variant; Weight; Work; addiction; behavior change; emerging adult; emerging adulthood; epidemiology study; gene discovery; genetic architecture; genetic epidemiology; genome wide association study; high risk; improved; indexing; interest; intervention program; novel; parent grant; parent project; personalized medicine; precision medicine; prevent; preventive intervention; programs; reduced substance use; response; risk variant; substance use; substance use treatment; trait

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.

项目摘要 这种行政补充，响应于非DA-24-003的物质使用快速翻译 以及成瘾的流行病学和预防干预研究，提出了转化发现的建议 来自父项目R01DA050721的出现“使用药物使用障碍的遗传结构 提前基因识别和对风险途径的理解”，以研究我们的通用的应用 流行病学发现是一种新型的预防干预措施，以减少风险的使用模式 新兴的成年人。家长项目有两个完整的目标：（1）进步发现所涉及的基因 在使用新的多元基因组技术的物质使用障碍中，（2）表征风险 与潜水纵向样本中确定的变体，跨发育以及与 环境。自父启动以来，我们在基因识别方面取得了巨大进步 R01，我们最近全基因组关联研究的结果约占差异的10％ 在独立样本中的物质使用和相关结果中。我们已经整合了产生的多基因 使用来自多个行为和环境风险因素的流行病学信息得分，使用来自多个的数据 多样化的纵向人群，以创建个体的风险估计，发现流行病学的结合 风险信息和遗传数据有意义地预测谁处于使用物质的风险较高 成年后的疾病。这项工作的理由是，它将为 个性化医学，提供个性化风险信息，有助于防止发展 问题和/或允许早期干预。通过此补品的行政资金，我们建议 （AIM 1）创建一个新的预防/干预计划，该计划包括一个在线平台的个人 通过整合有关其成瘾风险的个性化风险估计，通过整合有关其的信息而产生 基于父母赠款的研究，遗传，行为和环境风险因素，然后是 通过增加具有专业知识的新合作者的信息，有关如何降低风险的信息 行为改变； （AIM 2）与正在进入的成年人（18-25岁）进行小型RCT（n = 400） 高风险时期升级有风险的物质使用和问题的发展，以测试是否是否 个性化反馈计划的完成与危险物质使用的减少有关。这 项目是将遗传流行病学发现转化为预防干预措施的关键第一步。

项目成果

Correlates of suicidal behaviors and genetic risk among United States veterans with schizophrenia or bipolar I disorder.

患有精神分裂症或 I 型双相情感障碍的美国退伍军人自杀行为与遗传风险的相关性。

• DOI: 10.1038/s41380-024-02472-1
• 发表时间: 2024
• 期刊: Molecular psychiatry
• 影响因子: 11
• 作者: Bigdeli,TimB;Barr,PeterB;Rajeevan,Nallakkandi;Graham,DavidP;Li,Yuli;Meyers,JacquelynL;Gorman,BryanR;Peterson,RoseannE;Sayward,Frederick;Radhakrishnan,Krishnan;Natarajan,Sundar;Nielsen,DavidA;Wilkinson,AnnaV;Malhotra,Anil
• 通讯作者: Malhotra,Anil