Genetic Studies of Substance Abuse in Iowa Adoptees

描述(由申请人提供)：本次修订拨款申请的目的是筹集资金，以便在《爱荷华州收养研究》提供的有关物质使用障碍(SUD)的广泛流行病学数据中增加分子遗传成分。这些流行病学研究包括900多名成年被领养人，他们在出生时与亲生父母分开，在20年的时间里接受了采访，现在正在重新接受采访，重点是终身药物使用/滥用/依赖。在过去的二十年里，在对这些被领养人的研究中，我们的研究小组发现了显著的遗传和环境效应以及基因-环境相互作用，这些效应既影响药物滥用的早期生活风险因素，也影响成人药物使用/滥用/依赖的过程。收养范式通过检查遗传因素如何与收养家庭中的父母养育行为等环境因素相互作用，进一步研究了SUD危险行为的发展，并成为检测这些重要基因环境相互作用的研究设计的选择。在这一应用中，我们假设遗传变异性和某些基因环境相互作用是导致SUD易感性增加的原因，特别是尼古丁、酒精和大麻滥用/依赖。为了验证这一假设，我们将：1)进行后续的行为和认知评估(包括SUD风险的量化测量)，然后从我们特征良好的被领养人队列中收集DNA样本2)针对最有效的候选基因或基因座进行候选和单核苷酸多态分析，3)使用关联和多因素回归分析结果数据，创建单基因、基因*基因、环境和基因*环境对SUD易感性的可检验模型。作为这些实验的直接结果，我们将确定导致SUD易感性增加的特定基因和基因-环境相互作用。确定这些相互作用，特别是基因与环境的相互作用是重要的，因为这将允许开发更有效的生物和环境干预措施(例如，改变父母行为或制定新的行为治疗策略)，以治疗SUD。作为这些实验的间接结果，科学界将获得一种独特而宝贵的遗传资源，其他研究SUD遗传和流行病学脆弱性的研究人员可以利用该资源，证明这些爱荷华州通过NIDA遗传学联合会进行的收养研究。

DESCRIPTION (provided by applicant): The purpose of this revised grant application is to solicit funding to add a molecular genetic component to the extensive epidemiologic data on Substance Use Disorders (SUD) available in the Iowa Adoption Studies. These epidemiologic studies include over 900 adult adoptees, separated at birth from biologic parents, interviewed over a 20 year period, who are now being re-interviewed with a focus upon lifetime substance use/abuse/dependency. Over the past two decades in studies of these adoptees, our research group has shown significant genetic and environmental effects and gene-environment interactions that affect both early life risk factors for substance abuse and the course of adult substance use/abuse/dependency. The adoption paradigm has furthered the study of the development of risk behaviors for SUD by allowing the examination of how genetic factors may interact with environmental factors such as parenting behaviors in the adoptive home and is the study design of choice for the detection of these important gene environment interactions. In this application, we hypothesize that genetic variability and certain gene environment interactions are responsible for increased vulnerability to SUD, and in particular, Nicotine, Alcohol and Marijuana abuse/dependence. To test this hypothesis we will: 1) Conduct follow-up behavioral and cognitive assessments (including quantitative measures of SUD risk), then collect DNA samples from the our well characterized cohort of adoptees 2) conduct candidate and single nucleotide polymorphism analysis with respect to the best validated candidate genes or loci, and 3) analyze the resulting data using association and multifactorial regression to create a testable model of single gene, gene* gene, environmental and gene*environment contributions to the susceptibility to SUD. As direct result of these experiments, we will determine specific gene and gene-environment interactions that contribute to increased vulnerability to SUD. The identification of these interactions, and in particular gene x environment interactions, is important as it will allow the development of more effective biological and environmental (e.g. changing parenting behaviors or the formulation of new behavioral treatment strategies) interventions for the treatment of SUD. As an indirect result of these experiments, the scientific community will gain a unique and valuable genetic resource that can be utilized by other investigators of genetic and epidemiologic vulnerability to SUD in showing that these Iowa Adoption Studies through the NIDA Genetics Consortium.