MODELS FOR THE GENETIC EPIDEMIOLOGY OF CHRONIC DISEASES

不同的基因类型对慢性病的易感性往往不同。 阐明基因在疾病过程中所起的作用有助于 以了解其病因和开发治疗方法。然而，这个角色 可能会被相互作用的环境因素所掩盖 产生这种疾病的基因。环境变化可能 在具有相同基因的人中产生不同的表达； 由于基因的不同，环境可能与病例难以区分； 家庭内部共有的环境因素可能会模仿这种熟悉程度 是由基因引起的。与似然分析一起使用的遗传模型提供了 一种揭示基因效应并将它们与 对环境的影响。 这项研究建议派生和实现用于检测 遗传座位和环境因素对疾病终点和疾病的影响 生化标记物。主基因/多基因混合模型用于 检测有大影响的基因；将推导出近似值，以允许 二分和双变量表型数据的分析。通径分析 模型用来检验家族性环境效应.近似 将在家谱和基因存在的情况下进行应用 有很大的影响。这些模型将在计算机中实现 PAP程序(系谱分析包)，并通过做似然性测试 对现有家庭数据的分析。此外，人民行动党将继续 分发给其他用户，并使其更快、更易于使用。

Susceptibility to chronic disease often differs between genotypes. Elucidating the role the genotype plays in the disease process contributes to understanding its etiology and developing treatments. However, the role of the genotype may be obscured by environmental factors which interact with the genotype to produce the disease. Environmental variation may produce variable expression in persons with the same genotype; cases due to the environment may be indistinguishable from cases due to the genotype; environmental factors shared within households may mimic the familiality caused by genes. Genetic models used with likelihood analysis provide an approach to reveal the effects of genes and separate them from environmental effects. This research proposed to derive and implement models used to detect the effects of genetic loci and environmental factors on disease endpoints and biochemical markers. The major gene/polygenic mixed model is used to detect genes with large effects; approximations will be derived to allow analysis of dichotomous and bivariate phenotypic data. Path analysis models are used to test for familial environmental effects; approximations will be derived for application in pedigrees and in the presence of a gene with a large effect. The models will be implemented in the computer program PAP (Pedigree Analysis Package) and tested by doing likelihood analysis on available family data. In addition, PAP will continue to be distributed to other users and be made faster and easier to use.