title: Missing genetic information in case-control family data with general semi-parametric shared frailty model.
abstract: 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.
authors.affiliation: Faculty of Industrial Engineering and Management, Technion City, Haifa 32000, Israel. agraber@tx.technion.ac.il
authors.forename: Anna
authors.initials: A
authors.lastname: Graber-Naidich
authors.forename: Malka
authors.initials: M
authors.lastname: Gorfine
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Malone
authors.forename: Li
authors.initials: L
authors.lastname: Hsu
mesh_terms: D000328:Adult; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D003198:Computer Simulation; D005190:Family; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D008957:Models, Genetic; D015233:Models, Statistical; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human; C111164:BRAP protein, human; D044767:Ubiquitin-Protein Ligases