Statistical Methods in Genetic Studies of Substance Use

描述（由申请人提供）：从NIH指南PA-02-112“物质使用障碍的遗传流行病学”的出版物中可以明显看出，物质使用障碍（SUD）造成了严重的公共卫生和社会问题。基因-基因和基因-环境相互作用是了解SUD遗传流行病学的潜在重要因素。先进的数据分析和建模技术在这一奋进中变得不可或缺。分析进展通常被认为是复杂疾病遗传解剖的最大挑战之一。为了满足这一需求，NIH指南PA-02-112鼓励开发统计工具和分析方法，以增强我们对复杂表型（包括SUD）的理解。 这个应用程序响应这一特定的程序需要，通过开发统计方法，这是有用的解开复杂疾病的遗传基础。具体来说，我们的主要目标是开发，评估和应用新的统计模型（例如，潜在变量模型和基于树的模型）、方法和软件来进行复杂性状的遗传分析。我们对序数性状特别感兴趣，因为方法和软件几乎不存在。一旦确定了方法，将为所有这些模型开发配套软件，并在张博士的网站上向公众提供。 正如Zhang博士的小组过去所证明的那样，在开发方法的同时，我们将把它们应用于真实的数据，以解决重要的公共卫生问题，例如，与NIH指南PA-02-112的目标有关的问题。我们包括三个数据库，这将使我们能够研究各种问题。例如，我们将研究药物使用和酒精中毒的家庭传播中的潜在性别差异，并确定尼古丁依赖的候选基因，基因-基因和基因-环境相互作用。在我们的分析中，我们将考虑多种表型，包括酒精，药物和烟草使用以及共病的精神疾病，如焦虑。虽然应用的重点是遗传流行病学的SUB，我们的方法将是有用的理解复杂的序数性状一般。

DESCRIPTION (provided by applicant): As evident from the publication of NIH Guide PA-02-112 "Genetic Epidemiology of Substance Use Disorders," substance use disorders (SUDs) pose serious public health and societal problems. Gene-gene and gene-environment interactions are potentially important factors in understanding the genetic epidemiology of SUDs. Advanced data analysis and modeling techniques become indispensable in this endeavor. Analytic advancement is generally regarded as one of the greatest challenges in genetic dissection of complex disease. To address this need, NIH Guide PA-02-112 encourages development of statistical tools and analytic methods to enhance our understanding of complex phenotypes including SUDs. This application response to this specific programmatic need by developing statistical methods that is useful for unraveling the genetic basis of complex disorders. Specifically, our primary aim is to develop, evaluate, and apply new statistical models (e.g., latent variable models and tree-based models), methods, and software to conduct genetic analyses of complex traits. We are particularly interested in ordinal traits because methods and software virtually do not exist. Once the methodologies are established, companion software will be developed for all of these models and made available to the public on Dr. Zhang's website. While the methodologies are being developed, as Dr. Zhang's group has demonstrated in the past, we will apply them to real data to address important public health problems, for example, those pertinent to the objectives of NIH Guide PA-02-112. We include three databases, which will allow us to study a variety of issues. For example, we will examine the potential sex difference in familial transmission of drug use and alcoholism, and identify candidate genes, gene-gene and gene-environment interactions for nicotine dependence. In our analyses, we will consider multiple phenotypes including alcohol, drug, and tobacco use as well as comorbid psychiatric conditions such as anxiety. Although the focus of application is on genetic epidemiology of SUBs, our methodologies will be useful for understanding complex ordinal traits in general.