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.

项目总结

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