FAMILY BASED TESTS OF ASSOCIATION FOR COMPLEX DISEASES

复杂疾病协会基于家庭的测试

• 批准号: 2891153
• 负责人: NAN MCKENZIE LAIRD
• 金额: $ 34.76万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2001-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2891153
• 关键词: Alzheimer's disease; blood pressure; computer human interaction; computer program /software; computer simulation; epidemiology; family genetics; gene environment interaction; gene expression; gene interaction; genetic disorder; genetic markers; genetic susceptibility; handbook; human data; human population genetics; human subject; hypertension; linkage disequilibriums; linkage mapping; microtubules; online computer; phenotype; statistics /biometry

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.

该提案的长期目标是能够发现 使用基于家族的关联测试分析复杂性状背后的基因 检测连锁不平衡，同时防止虚假 由于人口混合而存在关联的证据。 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 对任意核心家庭实施基于家庭的关联测试 结构，包括缺少父母信息的结构；那可以 将环境协变量和多个基因纳入模型中； 可以测试基因-基因和基因-环境相互作用；还有那个 可应用于二分法、定量法和发病时间法 表型； (ii) 开发一个简单灵活的使用界面 程序和简单的安装程序，使程序得到广泛应用 可通过 ftp 获取； (iii) 检验统计特性 模拟和实际数据中的方法，并使用测试结果 制定该程序的使用指南； (iv) 开发在线 帮助系统和索引良好的用户手册；为用户提供支持 程序;并制定全面的统计文件 程序； (v) 扩展处理血统的方法 任意结构，包括缺少创始人信息的家庭。 由此产生的方法将能够测试候选基因，以测试 在存在关联的情况下进行链接，并测试关联 在已经建立联系的同质人群中（细 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 如果任意血统缺少父母信息，则多个 基因、协变量、基因-基因和基因-环境相互作用，以及 生存终点。