Disentangling unique etiologies of prescription opioid misuse and heroin use: Analysis of longitudinal, twin, and genomic data

解开处方阿片类药物滥用和海洛因使用的独特病因：纵向、双胞胎和基因组数据分析

• 批准号: 10311918
• 负责人: Genevieve Fullerton Dash
• 金额: $ 4.6万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10311918
• 关键词: Alcohols; Area; Behavior; Cessation of life; Clinical; Coin; Complex; Data; Drug usage; Environment; Epidemiology; Etiology; Faculty; Fellowship; Funding; Future; Genes; Genetic; Genetic Models; Genetic Risk; Genotype; Goals; Grant; Growth; Heritability; Heroin; Individual; Institution; Methods; Missouri; Modeling; Molecular; Monitor; Movement; National Institute of Drug Abuse; National Institute on Alcohol Abuse and Alcoholism; Nature; Opioid; Outcome; Pathway interactions; Phenotype; Population; Positioning Attribute; Psychology; Public Health; Registries; Reporting; Research; Research Design; Research Methodology; Respondent; Risk; Risk Factors; Role; Science; Side; Single Nucleotide Polymorphism; Source; Specificity; Statistical Methods; Subgroup; Surveys; Teacher Professional Development; Testing; Time; Training; Training Programs; Twin Multiple Birth; Twin Studies; United States; Universities; Wood material; Yang; addiction; base; cohort; design; drug use behavior; genetic approach; genetic risk factor; genome wide association study; genome-wide; genome-wide analysis; genomic data; heroin use; illicit drug use; illicit opioid; insight; inter-individual variation; longitudinal analysis; member; misuse of prescription only drugs; multiple drug use; neglect; novel; opioid epidemic; opioid exposure; opioid use; opioid use disorder; prescription opioid; prescription opioid misuse; prospective; psychologic; skill acquisition; substance use; trait

PROJECT SUMMARY/ABSTRACT Broad/Long Term Objectives: In line with NIDA’s positioning of the United States’ opioid crisis as a priority area of research, the broad goal of this project is to elucidate the nature of the association between prescription opioid misuse (POM) and heroin use. Integrating longitudinal and genetic methods, this study aims to identify the contribution (or lack thereof) of POM to entry into heroin use and to delineate potentially unique etiologies, courses, and correlates of POM and heroin use. Specific Aims: The aims of the proposed project are to identify distinct opioid use trajectories and their correlates; estimate heritability of and genetic correlations between POM, heroin use, and other forms of drug use in genomic data; and utilize multivariate twin modeling to test whether POM is more etiologically similar to other prescription misuse behavior than to heroin use. Research Design and Method: Longitudinal panel data from Monitoring the Future will be used to identify broad opioid use trajectories, trajectory subgroups, and movement between subgroups (e.g., POM to heroin use) over time via growth curve modeling, growth mixture modeling, and latent transition analysis. Genomic data from the National Epidemiologic Survey on Alcohol and Related Conditions-III will be used estimate heritability of POM and heroin use, and genetic correlations between 1) POM and heroin use, 2) POM and other prescription misuse, and 3) heroin use and other illicit drug use via genome-wide complex trait analysis. Australian Twin Registry Cohorts II and III will be used to test a multivariate twin model, which will incorporate several indicators of prescription misuse and illicit use to determine the extent to which specific and common genetic liability influence each phenotype. Significance: This project will advance understanding of the unique etiological mechanisms underlying risk for POM and heroin use, thereby better isolating factors contributing to the United States’ opioid crisis and informing multipronged public health approaches to mitigating the impact of opioids at the population level. Training Plan and Environment: The training plan is designed to provide the applicant with a rich program of training in advanced longitudinal and statistical genetic modeling, and their application to addiction science. Training will take place in the Department of Psychological Sciences at the University of Missouri, which has a highly reputed addiction training program funded by an NIAAA institutional training grant (T32; PI: Kenneth Sher); over 25% of the faculty in the department conduct substance use research. Fellowship training faculty were drawn from both clinical (Dr. Wendy Slutske [sponsor], Dr. Ian Gizer [co-sponsor]) and quantitative psychology (Dr. Phillip Wood [consultant]) training areas, and bring expertise in addiction research, longitudinal methods, and statistical genetics. External consultants (Drs. Arpana Agrawal, Elliot Nelson, and Rachel Winograd) will provide expertise on opioid use and use disorders. All external consultants are faculty members of nearby Missouri institutions and are University of Missouri affiliates, supporting a synergistic training environment.

项目总结/摘要 广泛/长期目标：符合NIDA将美国阿片类药物危机作为优先事项的定位 研究领域，本项目的广泛目标是阐明处方之间的关联性质 阿片类药物滥用（POM）和海洛因使用。结合纵向和遗传方法，本研究旨在确定 POM对进入海洛因使用的贡献（或缺乏），并描述潜在的独特病因， 课程，以及POM和海洛因使用的相关性。具体目标：拟议项目的目标是确定 不同的阿片类药物使用轨迹及其相关性;估计POM之间的遗传力和遗传相关性， 海洛因使用和其他形式的药物使用的基因组数据;并利用多变量双胞胎模型来测试是否 POM在病因学上与其他处方滥用行为比海洛因使用更相似。研究设计 方法：监测未来的纵向面板数据将用于确定广泛的阿片类药物使用 轨迹、轨迹子组，以及子组之间的移动（例如，POM到海洛因使用）， 增长曲线建模、增长混合建模和潜在转变分析。基因组数据来自国家 酒精及相关疾病的流行病学调查-III将用于估计POM和海洛因的遗传度 使用，以及1）POM和海洛因使用，2）POM和其他处方滥用，以及3） 使用海洛因和其他非法药物。澳大利亚双胞胎登记队列II 和III将用于测试多变量双胞胎模型，该模型将纳入处方的几个指标 滥用和非法使用，以确定具体和共同的遗传责任对每一种情况的影响程度 表型意义：该项目将促进对独特病因机制的理解 POM和海洛因使用的潜在风险，从而更好地隔离导致美国阿片类药物滥用的因素。 为减轻类阿片对人口的影响而采取的多管齐下的公共卫生办法 水平培训计划和环境：培训计划旨在为申请人提供丰富的课程 先进的纵向和统计遗传建模的培训，以及它们在成瘾科学中的应用。 培训将在密苏里州大学心理科学系进行， 由NIAAA机构培训补助金资助的高度知名的成瘾培训计划（T32; PI：Kenneth Sher）; 该系超过25%的教师进行物质使用研究。研究金培训教师是 来自临床（Wendy Slutske博士[申办者]，Ian Gizer博士[共同申办者]）和定量心理学 (Dr.菲利普伍德[顾问]）培训领域，并带来成瘾研究，纵向方法， 和统计遗传学。外部顾问（Arpana Agrawal、Elliot纳尔逊和Rachel Winograd博士）将 提供关于类阿片使用和使用障碍的专门知识。所有外部顾问都是附近 密苏里州机构和密苏里州附属大学，支持协同培训环境。