MODELS FOR THE GENETIC EPIDEMIOLOGY OF CHRONIC DISEASES

许多常见疾病虽然是家族性的，但似乎并不遵循简单的模式 继承权 在某些情况下，继承可能很简单，但 非遗传因素影响表型，从而掩盖了遗传 格局 例如，影响表型的环境因素可能 聚集在家庭中，导致非遗传的家族性。 多效性 基因可能对多种表型产生不一致的影响。 同配 交配可能会产生比预期更多的像父母的后代 假设是随机交配 表型表达可能需要一个环境 刺激，导致在其缺席的情况下减少的反射率。 老化可 促进表型的表达，模仿减少的遗传传递 给后代 同一基因型的表达在男性之间可能存在差异 和女性。 除非对这些表型的分析假设模型， 包括这些非遗传因素，遗传效应可能无法检测， 错误推断 本申请建议开发、实施和应用遗传模型 用于在非遗传因素存在的情况下检测主基因。 的 将在PAP中实现，PAP是一个用于概率的Fortran程序 分析. 提出的扩展包括回归模型的单变量 多变量表型、发病年龄曲线和不等方差 将继续为其他用户提供跨PAP服务。

Many common diseases, although familial, appear not to follow simple modes of inheritance. In some cases the inheritance may be simple, but nongenetic factors affect the phenotypes, thereby obscuring the genetic pattern. For example, environmental factors which affect the phenotype may aggregate in families, resulting in nongenetic familiality. Pleiotropic genes may produce inconsistent effects on multiple phenotypes. Assortative mating may produce more offspring resembling their parents than expected assuming random mating. Phenotypic expression may require an environmental stimulus, resulting in reduced penetrance in its absence. Aging may promote expression of the phenotype, mimicking reduced genetic transmission to offspring. The expression of the same genotype may differ between males and females. Unless the analyses of such phenotypes assume models which include these nongenetic factors, the genetic effect may be undetectable or falsely inferred. This application proposes to develop, implement, and apply genetic models used to detect major genes in the presence of nongenetic factors. The implementation will occur in PAP, a Fortran program for likelihood analysis. The extensions proposed include regressive models for univariate and multivariate phenotypes, age of onset curves, and unequal variances across PAP for other users will be continued.