Failure Time Methods for Family Disease Studies

BACKGROUND:

In the study of chronic diseases, both environmental and genetic factors can be influential. In highly common diseases, such as coronary heart disease, genetic effects may be more influential in determining the age of onset of the disease than in determining whether or not one gets the disease. When sufficient information is available, family studies can help localize possible disease genes on the human chromosome through genetic linkage analysis, and familial aggregation of disease can help separate the effects of inheritance, environment and lifestyle on the risk of disease.

DESIGN NARRATIVE:

The study developed: (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) was applied to a family study of cardiovascular disease and a twin study of appendectomy. Method (2) was applied to ongoing genetic studies conducted at the University of California at San Francisco. Method (3) was applied to a family study of coronary heart disease in Western Australia. Well-documented, user-friendly programs were developed and made publicly available.