Gene-Environment Interaction for Cannabis Use Disorders in Blacks and Whites in the U.S.

美国黑人和白人大麻使用障碍的基因与环境相互作用

• 批准号: 9093722
• 负责人: Jacquelyn Leigh Meyers
• 金额: $ 11.65万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9093722
• 关键词: Accounting; Address; Adult; African American; Alcohol or Other Drugs use; Alcohols; American; Area; Automobile Driving; Behavior; Biological; Cannabinoids; Cannabis; Consultations; DSM-IV; Data; Dependence; Development; Dopamine; Environmental Exposure; Environmental Risk Factor; Epidemiologic Studies; Epidemiology; Ethnic group; Etiology; European; Event; Exposure to; Frequencies; Gene Frequency; Genetic; Genetic Predisposition to Disease; Genetic Risk; Genetic Variation; Genetic study; Genotype; Geographic state; Glycine; Goals; Health; Heterogeneity; Interdisciplinary Study; Lead; Life; Linkage Disequilibrium; Measurement; Measures; Medical; Mentors; Mentorship; Modification; N-Methylaspartate; National Institute of Drug Abuse; Neurobiology; Neurosciences; Outcome; Pathway interactions; Pattern; Periodontal Diseases; Phenotype; Policies; Population; Prevalence; Preventive Intervention; Productivity; Psychology; Psychosocial Factor; Psychotic Disorders; Reporting; Research; Research Personnel; Research Training; Risk; Role; Sampling; Social Environment; Stress and Coping; Structure; Surveys; Symptoms; System; Testing; Time; Training; Trauma; Universities; addiction; base; biological systems; experience; gamma-Aminobutyric Acid; gene environment interaction; genetic association; genetic variant; illicit drug use; marijuana use; marijuana use disorder; marijuana user; meetings; neuropsychological; psychologic; racial and ethnic; racial difference; racial diversity; resilience; response; social; traumatic event

 DESCRIPTION (provided by applicant): Gene-Environment Interaction for Cannabis Use Disorders in Blacks and Whites in the US. 40-50% of US adults have used cannabis, and ~1/3 of users experience at least one cannabis use disorder (CUD) symptom which increases risk for many negative outcomes, including problematic substance use behaviors (SUB). Recent data has shown that the prevalence of CUD is growing faster among African- Americans (AA) than all other groups in the US. There are critical gaps in US SUB etiology that gene- environment interaction (GxE) research can begin to address: (1) There are no large-scale genetic studies of CUD in AAs, creating a gap in understanding the genetic etiology of CUD in the US. AAs have greater genetic diversity than Whites/European Americans (EA) due to evolutionary differences in allele frequencies and linkage disequilibrium (LD). Thus, genetic association studies comparing AAs and EAs are critically needed to further understanding in AAs generally, and in the US. Social context (trauma, religiosity) modifies the strength of genetic risk for SUB. However, (2) there are no GxE studies of CUD. Moreover, few studies examine GxE of SUB in AAs, and no study has examined if GxE effects of SUB differ between AAs and EAs, which might be expected due to known AA/EA differences in ancestry, rates and types of exposure to trauma and religiosity, and impact on SUB. (3) GxE research on CUD has yet to employ new developments in polygenic strategies that incorporate known biological systems. To date, only two studies of any SUB used polygenic strategies in the context of GxE, mainly because few studies have sufficiently large samples needed, and concerns about the non-translatability of polygenic scores into specific genetic/neurobiological targets. These concerns are mitigated with pathway-based set tests, which aggregate genetic variants across candidate biological pathways to better reflect the underlying structure of CUD. The revised K01 proposal delineates the training required for me to become an independent investigator conducting interdisciplinary research that identifies the mechanisms via which psychosocial factors modify genetic and neurobiological risk for SUB in the diverse US population. My research will examine if trauma and/or religiosity modifies genetic risk for CUD in both AAs and EAs in a new US nationally representative sample, the NESARC-III (n=36,309; 20%:7,262 AA), which includes genotypic data and dimensional measures of cannabis use frequency, and DSM-IV and 5 CUD. Three areas of advanced training will enable me to carry out these goals: (1) Phenotypic Measurement of SUB, (2) Addictions Neuroscience, and (3) Trauma and Resilience. The proposed activities are ambitious, but feasible, given my record of productivity, mentorship by an interdisciplinary team of experts (Hasin (primary mentor), Martinez, Koenen) at Columbia University, consultation with Dr. Agrawal in CUD Genetics and Dr. Fullilove in the Responsible Presentation of Genetic Differences by Race, and K01 protected time (5 yrs) for research and training, and the development of an R01.

 描述（由申请人提供）：美国黑人和白人大麻使用障碍的基因与环境相互作用。40-50% 的美国成年人使用过大麻，约 1/3 的使用者患有至少一种大麻使用障碍 (CUD)。 ) 症状，增加了许多负面结果的风险，包括有问题的物质使用行为 (SUB)。最近的数据显示，非洲裔美国人 (AA) 的 CUD 患病率增长速度快于美国所有其他群体。美国 SUB 病因学中存在一些关键差距，基因-环境相互作用 (GxE) 研究可以开始解决：(1) AA 中没有针对 CUD 的大规模遗传学研究，这在了解 AA 中 CUD 的遗传病因学方面存在差距。由于等位基因频率和连锁不平衡 (LD) 的进化差异，美国 AA 比白人/欧洲裔美国人 (EA) 具有更大的遗传多样性，因此，迫切需要比较 AA 和 EA 的遗传关联研究以进一步了解。一般而言，在 AA 中，以及在美国，社会背景（创伤、宗教信仰）改变了 SUB 的遗传风险强度，但是，(2) 没有针对 CUD 的 GxE 研究，并且很少有研究考察 SUB 的 GxE。没有研究检验 SUB 的 GxE 效应在 AA 和 EA 之间是否存在差异，这可能是预期的，因为已知 AA/EA 在血统、遭受创伤和宗教的比率和类型以及影响方面存在差异(3) CUD 的 GxE 研究尚未采用纳入已知生物系统的多基因策略的新进展，迄今为止，只有两项研究在 GxE 的背景下使用了多基因策略，这主要是因为很少有研究具有足够大的规模。所需的样本，以及对多基因评分不可转化为特定遗传/神经生物学目标的担忧通过基于途径的集合测试得到缓解，这些测试汇总了候选生物途径的遗传变异，以更好地反映修订后的 CUD 的基本结构。 K01 提案描述了我成为一名独立调查员所需的培训，该研究旨在确定心理社会因素改变美国不同人群的 SUB 遗传和神经生物学风险的机制。我的研究将检查创伤和/或宗教信仰是否会改变遗传风险。在新的美国全国代表性样本 NESARC-III（n=36,309；20%：7,262 AA）中，针对 AA 和 EA 中的 CUD，其中包括大麻使用频率的基因型数据和维度测量，以及 DSM-IV 和 5 CUD 的三个高级培训领域将使我能够实现这些目标：(1) SUB 表型测量，(2) 成瘾神经科学，以及 (3)创伤和复原力。考虑到我的生产力记录、哥伦比亚大学跨学科专家团队（哈辛（主要导师）、马丁内斯、科宁）的指导，以及与我的咨询，拟议的活动是雄心勃勃的，但也是可行的。 CUD 遗传学的 Agrawal 博士和按种族和 K01 负责任地展示遗传差异的 Fullilove 博士保护了研究和培训以及 R01 开发的时间（5 年）。