Missing genetic information in case-control family data with general semi-parametric shared frailty model
- 97 Downloads
Case-control family data are now widely used to examine the role of gene-environment interactions in the etiology of complex diseases. In these types of studies, exposure levels are obtained retrospectively and, frequently, information on most risk factors of interest is available on the probands but not on their relatives. In this work we consider correlated failure time data arising from population-based case-control family studies with missing genotypes of relatives. We present a new method for estimating the age-dependent marginalized hazard function. The proposed technique has two major advantages: (1) it is based on the pseudo full likelihood function rather than a pseudo composite likelihood function, which usually suffers from substantial efficiency loss; (2) the cumulative baseline hazard function is estimated using a two-stage estimator instead of an iterative process. We assess the performance of the proposed methodology with simulation studies, and illustrate its utility on a real data example.
KeywordsCase-control family study Missing genotypes Multivariate survival analysis Frailty model
Unable to display preview. Download preview PDF.
- Cox DR (1972) Regression models and life tables (with discussion). J R Stat Soc B 34: 187–220Google Scholar
- Gill RD (1985) Discussion of the paper by D. Clayton and J. Cuzick. J R Stat Soc A 148: 108–109Google Scholar
- Malone KE, Daling JR, Doody DR, Hsu L, Bernstein L, Coates RJ, Marchbanks PA, Simon MS, McDonald JA, Norman SA, Strom BL, Burkman RT, Ursin G, Deapen D, Weiss LK, Folger S, Madeoy JJ, Friedrichsen DM, Suter NM, Humphrey MC, Spirtas R, Ostrander EA (2006) Prevalence and predictors of BRCA1 and BRCA2 mutations in a population-based study of breast cancer in white and black American women ages 35 to 64 years. Cancer Res 66: 8297–8308CrossRefGoogle Scholar