Disease Comorbidity and Survival in the NHLBI Family Heart Study
Principal Investigator: Michael Province, Ph.D.
September 1, 2001 - August 31, 2002

Study Questions:
1. What is the exact amount of excess familial clustering within each family for each risk factor/disease condition?
2. How do these familial factors co-cluster (or not) within the same families?
3. What increased/decreased risk do combinations of family-specific clustering confer on overall/disease specific survival?
4. What is the independent contribution to survival risk from the familial nature of each factor?

Objectives:
--To quantify the extent of familial clustering of families for each comorbidity and risk factor
--To characterize the excess sharing of familial risk for clusters of diseases
--To assess the independent contribution of these to overall survival

Study Methodology:
National Death Index (NDI) searches will be conducted to update current vital status. The relationship between prevalent disease and survival within individuals as well as within pedigree units will be examined using a variety of state of the art statistical models . Family Risk Score (FRS) methods (Williams et al., 2001) will allow us to quantify the extent of excess familial clustering of each family for each co-morbid condition. The degree to which these FRS scores are correlated across disease conditions within the same families will allow us to characterize the excess sharing of familial risk for clusters of diseases. We have also developed extensions of statistical frailty models for families (Siegmund et al., 1998, 1999) and bootstrapping methods (Province et al., 2000, 2001), which will allow us to assess the impact of disease and risk factors on survival in related (non-independent) samples. Finally, our general structural equations software designed for familial and genetic quantitative traits (SEGPATH: Province et al., 1995; 2001) will be extended to include survival.