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》的出版中可以明显看出，物质使用障碍(SODS)会造成严重的公共卫生和社会问题。基因-基因和基因-环境相互作用是理解SUDS遗传流行病学的潜在重要因素。在这一努力中，先进的数据分析和建模技术变得不可或缺。分析进展通常被认为是复杂疾病基因解剖中最大的挑战之一。为了满足这一需求，美国国立卫生研究院PA-02-112指南鼓励开发统计工具和分析方法，以加强我们对包括肥皂症在内的复杂表型的理解。 这一应用程序通过开发有助于解开复杂疾病的遗传基础的统计方法来响应这一特定的程序需求。具体地说，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，因为方法和软件实际上并不存在。一旦建立了方法学，将为所有这些模型开发配套的软件，并在张博士的网站上向公众提供。 在开发方法的同时，正如张博士的团队过去所展示的那样，我们将把它们应用于实际数据，以解决重要的公共卫生问题，例如与NIH指南PA-02-112目标相关的问题。我们包括三个数据库，这将使我们能够研究各种问题。例如，我们将研究吸毒和酗酒在家族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，我们将考虑包括酒精、药物和烟草使用在内的多种表型，以及焦虑等共病精神疾病。虽然应用的重点是Subs的遗传流行病学，但我们的方法将有助于从总体上理解复杂的有序性状。

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.