FAMILY BASED TESTS OF ASSOCIATION FOR COMPLEX DISEASES

这项提议的长期目标是能够发现 利用基于家系的关联测试研究复杂性状的基因 在检测链接不平衡的同时防止虚假 由于人口混杂而产生关联的证据。为了实现这一目标， 该项目的具体目标是：(I)开发计算机程序， 使用任意核心家庭实现基于家庭的关联测试 结构，包括缺少父母信息的那些；它可以 将环境协变量和多个基因纳入模型； 可以测试基因与基因和基因与环境的相互作用； 可用于二分、定量和发病时间 表型；(Ii)开发一个简单而灵活的使用界面 程序和简单的安装程序，并使程序范围广泛 可通过ftp获得；(Iii)测试 在模拟和真实数据中的方法，并使用测试结果 制定使用该方案的指导方针；(Iv)开发一个网上 帮助系统和索引良好的用户手册；为用户提供支持 计划；并编制全面的统计文件 程序；以及(V)扩大处理家系的方法 任意结构，包括缺少创始人信息的家庭。 由此产生的方法学将能够测试候选基因，测试 在存在关联的情况下进行链接，并测试关联 在已经建立了连锁的同质种群中(很好 映射)。调查人员还表示，新计算机 软件将填补基于家庭的关联测试的空白，特别是 在任意谱系缺少父母信息的情况下，多个 基因、协变量、基因与基因和基因与环境的相互作用 生存的终点。

The long-term objective of this proposal is to enable the discovery of genes underlying complex traits using family based association tests that detect linkage disequilibrium while protecting against spurious evidence of association due to population admixture. To achieve this, specific aims of this project are to: (i) develop computer program that implements family based association tests with arbitrary nuclear family structure including those with missing parental information; that can incorporate environmental covariates and multiple genes into the model; that can test for gene-gene and gene-environment interactions; and that may be applied to dichotomous, quantitative, and time-of-onset phenotypes; (ii) develop a simple and flexible use interface to the program and easy installation procedures, and make the program widely available via ftp; (iii) test the statistical properties of the methodology in simulations and in real data, and use the test results to develop guidelines for the use of the program; (iv) develop an online help system and well-indexed user's manual; provide user support for the program; and develop comprehensive documentation of the statistical procedures; and (v) to extend the methodology to handle pedigrees of arbitrary structure including families with missing founder information. The resulting methodology will be able to test candidate genes, to test for linkage in the presence of association, and to test for association in homogeneous populations where linkage has been established (fine mapping). The investigators also indicate that the new computer software will fill gaps in family based association tests, specifically in cases with arbitrary pedigrees missing parental information, multiple genes, covariates, gene-gene and gene-environment interactions, and survival end-points.