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.

项目摘要/摘要 广泛/长期目标：符合NIDA对美国阿片类危机的定位作为优先事项 研究领域，该项目的广泛目标是阐明处方之间的关联性质 Oopioid Missuse（POM）和海洛因使用。整合纵向和遗传学方法，本研究旨在确定 POM对进入海洛因使用的贡献（或缺乏）贡献，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。具体目的：拟议项目的目的是确定 独特的阿片类药物使用轨迹及其相关性；估计POM之间的遗传和遗传相关性 海洛因的使用以及基因组数据中的其他形式的药物使用；并利用多元双建模来测试是否 POM在病因上与其他处方行为更相似，而不是使用海洛因。研究设计 和方法：监视未来的纵向面板数据将用于识别广泛的阿片类药物使用 随着时间的流逝 生长曲线建模，生长混合物建模和潜在过渡分析。来自国家的基因组数据 关于酒精和相关条件的流行病学调查 - 将使用POM和海洛因的遗传力估计 1）POM和海洛因使用之间的使用以及遗传相关性，2）POM和其他处方Massuse，以及3） 海洛因使用和其他非基因组复杂性状分析的非法药物使用。澳大利亚双胞胎注册人群II III将用于测试多元双胞胎模型，该模型将包含几个处方指标 滥用和非法使用以确定特定和常见的遗传责任的程度 表型。意义：该项目将提高对独特的病因机制的理解 POM和海洛因使用的潜在风险，从而更好地隔离因素，导致美国阿片类药物 危机和通知多收益的公共卫生方法，以减轻阿片类药物对人群的影响 等级。培训计划和环境：培训计划旨在为申请人提供丰富的计划 高级纵向和统计遗传建模的培训及其在成瘾科学上的应用。 培训将在密苏里大学的心理科学系进行 由NIAAA机构培训补助金（T32; PI：Kenneth Sher）资助的高度再现成瘾培训计划； 该系中有25％以上的教职员工进行药物使用研究。奖学金培训教师是 摘自临床（Wendy Slutske博士[赞助商]，Ian Gizer博士[共同发起人]）和定量心理学 （Phillip Wood博士[顾问]）培训领域，并为成瘾研究，纵向方法带来专业知识， 和统计遗传学。外部顾问（Arpana Agrawal博士，Elliot Nelson和Rachel Winograd）将 提供有关阿片类药物使用和使用障碍的专业知识。所有外部顾问都是附近的教职员工 密苏里州机构和密苏里大学的分支机构，支持协同的培训环境。