Physical Sciences and Mathematics Commons^™

Modeling Sequential Event Times Using Family Data, Balakumar Swaminathan

Electronic Thesis and Dissertation Repository

In genetic epidemiology, families harboring certain genetic mutations are predisposed to successive cancers in their lifetime. This thesis aims to provide reliable estimates of relative risk and age-dependent cumulative risks (penetrance) associated with the mutated gene for successive cancers. We develop a statistical framework for modeling sequential event times arising from family data. A shared frailty model is employed to incorporate the dependence between the two event times. Because families are ascertained through non-random sampling, an ascertainment-corrected retrospective likelihood approach is proposed to account for the non-ignorable sampling design. Simulation studies demonstrate that our proposed method provides unbiased and reliable …