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.

项目概要 本行政补充，针对 NOT-DA-24-003 物质使用快速转换而提交 和成瘾流行病学和预防干预研究，建议转化研究结果 来自母项目 R01DA050721“利用物质使用障碍的遗传结构来 基因识别和理解风险进展的途径”来研究我们的遗传基因的应用 流行病学发现作为一种新的预防干预措施，可减少人群中危险的物质使用模式 母项目有两个互补的目标：（1）推进相关基因的发现。 使用新的多变量基因组技术来研究物质使用障碍，以及（2）描述风险特征 与不同纵向样本中已识别的变异相关，跨越发展，并结合 自从父母诞生以来，我们在基因鉴定方面取得了巨大的进步。 R01，我们最近的全基因组关联研究的结果约占方差的 10% 我们整合了独立样本中的物质使用和相关结果。 使用来自多个方面的数据，对行为和环境风险因素的流行病学信息进行评分 不同的纵向队列，以创建个体风险估计，发现流行病学的结合 风险信息和遗传数据有助于预测谁的药物使用风险较高 从事这一工作的理由是，它将为成年初期的疾病奠定基础。 个性化医疗，提供个性化风险信息，有助于预防疾病的发展 问题和/或允许早期干预，我们建议利用该补充的行政资金 （目标 1）创建一个新的预防/干预计划，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评估，该评估是通过整合有关他们的信息而生成的 基于家长资助的研究的遗传、行为和环境风险因素，然后是 关于如何降低风险的信息，通过增加具有以下专业知识的新合作者而开发 行为改变；以及（目标 2）对正在进入的新兴成年人（18-25 岁）进行小型随机对照试验 (N=400) 危险物质使用升级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。 该项目是将遗传流行病学发现转化为预防干预的关键第一步。

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