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: 9117932
• 负责人: Jacquelyn Leigh Meyers
• 金额: $ 11.66万
• 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/9117932
• 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; Drug usage; 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; Illicit Drugs; 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; 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; marijuana use; marijuana use disorder; marijuana user; meetings; neuropsychological; preventive intervention; psychologic; racial and ethnic; racial difference; 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（由适用提供）：美国黑人和白人的大麻使用障碍的基因 - 环境相互作用。美国成年人中有40-50％使用大麻，〜1/3的用户至少经历了一种大麻使用障碍（CUD）症状，这增加了许多负面结果的风险，包括有问题的药物使用行为（SUB）。最近的数据表明，在非裔美国人（AA）中，CUD的患病率比美国所有其他群体都要快。在美国亚病因中，基因环境相互作用（GXE）的研究可以开始解决：（1）AAS中没有大规模的CUD遗传研究，从而在美国的CUD遗传学遗传学方面存在差距。由于等位基因频率的进化差异和连锁二动物（LD）的进化差异，AA的遗传多样性比白人/欧洲人（EA）更大。这是需要比较AAS和EAS的遗传关联研究，以便在AAS和美国进行进一步了解。社会背景（创伤，宗教信仰）改变了亚遗传风险的力量。但是，（2）没有GXE研究。此外，很少有研究检查AAS中的Sub的GXE，并且没有研究检查AAS和EAS之间的GXE差异的影响，这可能是由于已知的AA/EA/EA在祖先的差异，对创伤和宗教信仰的影响以及对Sub的影响而预期的。 （3）GXE对CUD的研究尚未使纳入已知生物系统的多基因策略的新发展。迄今为止，在GXE背景下，只有两项对任何子使用多基因策略的研究，主要是因为很少有研究需要足够大的样本，并且担心多基因分数将多基因分数转化为特定的遗传/神经生物学靶标。这些问题是通过基于途径的集合测试来缓解这些问题的，这些测试将跨候选生物学途径的遗传变异汇总，以更好地反映CUD的潜在结构。修订后的K01提案描述了我成为进行跨学科研究的独立研究人员所需的培训，该研究人员识别了通过这种机制来修改美国潜水员人群中SUB的遗传和神经生物学风险的机制。我的研究将检查创伤和/或宗教是否会改变美国新的全国代表性样本中AA和EAS的遗传风险，Nesarc-III（n = 36,309; 20％：20％：7,262 AA），其中包括基因型数据和大麻使用频率以及DSM-IV和DSM-IV和DSM-IV和5 cud和5 cud。高级培训的三个领域将使我能够实现这些目标：（1）SUB，（2）成瘾神经科学的表型测量，以及（3）创伤和韧性。鉴于我在哥伦比亚大学的跨学科专家团队（Hasin（主要导师），Martinez，Koenen）的跨学科专家团队（Hasin（主要导师），Martinez，Koenen）的心态，与Agrawal in Cud遗传学和Fullilove博士的咨询，对种族和K01的遗传差异进行了培训（5 Y YRS）的遗传差异（5 YRS），这是雄心勃勃但可行的，但可行。