FAILURE TIME METHODS FOR FAMILY DISEASE STUDIES

说明(申请人摘要)：本研究的长期目标 是发展完善的方法学，这将有助于研究 遗传和环境因素在心血管疾病中的作用。这个 该提案的短期目标是制定年龄统计方法 疾病发病率的基于人群的家庭研究的发病数据。这个 这类研究的方法必须适应审查、半参数建模 和家族关系。需要进一步开发能够 模型复杂依赖结构及检验其适合性的方法 数据的参数相关性模型。因此，这一行动的具体目标是 建议发展为：(1)评估适合性的一般战略 发病年龄家庭聚集性的参数依赖模型； (2)一种计算简单的年龄遗传连锁分析方法 起效数据；(3)新近开发的添加剂的应用和说明 复杂家庭依赖结构的脆弱性模型。方法(1)将为 应用于心血管疾病的家族研究和双胞胎研究 阑尾切除术。方法(2)将应用于正在进行的遗传研究 在加州大学旧金山分校。方法(3)将应用于冠心病的家系研究 在西澳大利亚。将开发文档齐全、用户友好的程序 并公之于众。

DESCRIPTION (Applicant's abstract) : The long-term objective of this research is the development of sound methodologies which will facilitate studying the role of both genetic and environmental factors in cardiovascular disease. The short term goal of the proposal is to develop statistical methods for age at onset data from population-based family studies of disease incidence. The methods for such studies must accommodate censoring, semi-parametric modeling and familial correlations. Further development is needed for methods which can model complex dependence structures and methods which can examine the fit of parametric dependence models to data. Accordingly, the specific aims of this proposal are development of: (1) a general strategy for evaluating the fit of parametric dependence models for familial clustering of ages at disease-onset; (2) a computationally simple method for genetic linkage analysis of age at onset data; (3) application and illustration of recently developed additive frailty models for complex familial dependence structures. Method (1) will be applied to a family study of cardiovascular disease and a twin study of appendectomy. Method (2) will be applied to ongoing genetic studies conducted at UCSF. Method (3) will be applied to a family study of coronary heart disease in Western Australia. Well-documented, user-friendly programs will be developed and made publicly available.