Genetic & environmental pathways to drug use, abuse & dependence

遗传

• 批准号: 8309440
• 负责人: Nathan Alexander Gillespie
• 金额: $ 24.27万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8309440
• 关键词: Address; Adolescent; Age; Area; Australia; Award; Cannabis; Cannabis Abuse; Clinical; Communities; Comorbidity; Complex; Consumption; DSM-IV; Data; Dependence; Development; Diagnosis; Disease; Drug Addiction; Drug Use Disorder; Drug usage; Environment; Epidemiology; Family; Frequencies; Funding; Future; Genetic; Genotype; Goals; Health; Heterogeneity; High Prevalence; Household; Illicit Drugs; Individual; Individual Differences; Interview; Investments; Knowledge; Lead; Life Cycle Stages; Location; Marijuana Dependence; Measures; Mental Health; Mental disorders; Methodology; Modeling; Pathway interactions; Pattern; Personal Satisfaction; Pharmaceutical Preparations; Phenotype; Policies; Population; Prevalence; Probability; Quantitative Trait Loci; Relative (related person); Reporting; Research; Respondent; Risk; Risk Factors; Running; Sampling; Schizophrenia; Siblings; Structure; Surveys; Testing; Time; Translating; Twin Multiple Birth; Weight; aged; base; cost; cost effective; gene discovery; genetic epidemiology; genetic linkage analysis; genome wide association study; genome-wide linkage; improved; macula; novel; population based; response; social; success; theories; trait

DESCRIPTION (provided by applicant): The goal of this project is to make a significant contribution to the discovery of genes influencing cannabis use disorders (CUD). Given the widespread use of cannabis, increasing recognition of the potential health effects of this drug, and a growing recognition of CUDs as distinct clinical entities, this application seeks funding to conduct clinical interviews on a large sample of Australian twins and their non-twin siblings, and run genome wide linkage and individual genome wide association scan (WGAS) to detect quantitative trait loci (QTL) for CUDs. The specific aims are: Aim 1: To fund structured clinical interviews in order to obtain item level data and DSM-IV diagnoses of cannabis abuse and dependence on 1000 Australian twins and their non-twin siblings from the Brisbane Adolescent Twin Sample. Item level data and DSM-IV diagnoses for other drugs, as well as measures of lifetime patterns of drug use, drug use disorders, and contextual and developmental risk factors for CUD phenotypes will also be obtained. Using the same model fitting strategy proposed in the K99 (see Section 4.D.3.2.4), these data will allow us to determine whether the best fitting empirical CUD phenotypes based on MATR data, provide a good fit to the Australian data.; Aim 2: Identify QTLs for CUDs using genome wide linkage analyses based on 1000 individuals from 460 families, followed by individual WGAS analyses on 3000 individuals. The damage to individuals and the social cost to the community caused by CUDs are enormous. The identification of QTLs responsible for CUDs is required to fill gaps in our knowledge, to develop targeted treatments, and to provide an empirical basis for addressing policy issues and public concerns about the cause of cannabis use disorders. By capitalizing on the US and Australian data, Dr Gillespie is also proposing, as part of future analyses, a number of enormously cost-effective opportunities to test novel research questions and specific hypotheses which will improve our understanding of drug use disorders. These will enable us to determine the degree to which genetic liability to CUDs can be explained by the same QTLs responsible for liability to other drug use disorders and/or psychiatric disorders.

描述（由申请人提供）：该项目的目标是为发现影响大麻使用障碍（CUD）的基因做出重大贡献。鉴于大麻​​的广泛使用，人们越来越认识到这种药物对健康的潜在影响，以及越来越多地认识到 CUD 作为独特的临床实体，本申请寻求资金对澳大利亚双胞胎及其非双胞胎兄弟姐妹的大样本进行临床访谈，并运行全基因组连锁和个体基因组广泛关联扫描 (WGAS)，以检测 CUD 的数量性状位点 (QTL)。具体目标是： 目标 1：资助结构化临床访谈，以获得来自布里斯班青少年双胞胎样本的 1000 名澳大利亚双胞胎及其非双胞胎兄弟姐妹的大麻滥用和依赖的项目级数据和 DSM-IV 诊断。还将获得其他药物的项目级数据和 DSM-IV 诊断，以及药物使用终生模式、药物使用障碍以及 CUD 表型的背景和发育风险因素的测量。使用 K99 中提出的相同模型拟合策略（参见第 4.D.3.2.4 节），这些数据将使我们能够确定基于 MATR 数据的最佳拟合经验 CUD 表型是否能够很好地拟合澳大利亚数据。目标 2：使用基于 460 个科的 1000 名个体的全基因组连锁分析来识别 CUD 的 QTL，然后对 3000 名个体进行单独的 WGAS 分析。 CUD 对个人造成的损害以及对社区造成的社会成本是巨大的。需要鉴定导致 CUD 的 QTL，以填补我们的知识空白，开发有针对性的治疗方法，并为解决政策问题和公众对大麻使用障碍原因的担忧提供经验基础。通过利用美国和澳大利亚的数据，吉莱斯皮博士还提出，作为未来分析的一部分，许多极具成本效益的机会来测试新的研究问题和具体假设，这将增进我们对吸毒障碍的理解。这些将使我们能够确定对 CUD 的遗传责任可以在多大程度上通过与其他药物使用障碍和/或精神疾病的责任相同的 QTL 来解释。

项目成果

Dynamic networks of psychological symptoms, impairment, substance use, and social support: The evolution of psychopathology among emerging adults.

• DOI: 10.1192/j.eurpsy.2022.23
• 发表时间: 2022-06-13
• 期刊: EUROPEAN PSYCHIATRY
• 影响因子: 7.8
• 作者: Crouse, Jacob J.;Ho, Nicholas;Scott, Jan;Parker, Richard;Park, Shin Ho;Couvy-Duchesne, Baptiste;Mitchell, Brittany L.;Byrne, Enda M.;Hermens, Daniel F.;Medland, Sarah E.;Martin, Nicholas G.;Gillespie, Nathan A.;Hickie, Ian B.
• 通讯作者: Hickie, Ian B.

Days out of role and somatic, anxious-depressive, hypo-manic, and psychotic-like symptom dimensions in a community sample of young adults.

• DOI: 10.1038/s41398-021-01390-y
• 发表时间: 2021-05-13
• 期刊: Translational psychiatry
• 影响因子: 6.8
• 作者: Crouse JJ;Ho N;Scott J;Martin NG;Couvy-Duchesne B;Hermens DF;Parker R;Gillespie NA;Medland SE;Hickie IB
• 通讯作者: Hickie IB

Can network analysis of self-reported psychopathology shed light on the core phenomenology of bipolar disorders in adolescents and young adults?

• DOI: 10.1111/bdi.13067
• 发表时间: 2021-09
• 期刊: Bipolar disorders
• 影响因子: 5.4
• 作者: Scott J;Crouse JJ;Ho N;Carpenter J;Martin N;Medland S;Parker R;Byrne E;Couvy-Duchesne B;Mitchell B;Merikangas K;Gillespie NA;Hickie I
• 通讯作者: Hickie I

The Genetic Relationship Between Psychological Distress, Somatic Distress, Affective Disorders, and Substance Use in Young Australian Adults: A Multivariate Twin Study.

澳大利亚年轻人的心理困扰、躯体困扰、情感障碍和药物使用之间的遗传关系：一项多变量双胞胎研究。

• DOI: 10.1017/thg.2018.33
• 发表时间: 2018
• 期刊: Twin research and human genetics : the official journal of the International Society for Twin Studies
• 作者: Chang,Lun-Hsien;Couvy-Duchesne,Baptiste;Medland,SarahE;Gillespie,NathanA;Hickie,IanB;Parker,Richard;Martin,NicholasG
• 通讯作者: Martin,NicholasG