Using Family Members to Augment Genetic Case-Control Studies of a Life-Threatening Disease

• Activity Number: 92
• Type: Invited
• Date/Time: Sunday, August 4, 2013 : 8:30 PM to 10:30 PM
• Sponsor: Section on Statistics in Epidemiology
• Author(s): Lu Chen*+ and Jinbo Chen and Clarice R. Weinberg
• Companies: University of Pennsylvania and University of Pennsylvania School of Medicine and National Institute of Environmental Health
• Keywords: Case-control genetic association study ; Survival bias ; Missing data ; Family genetic data ; Retrospective maximum likelihood

Abstract

Survival bias may arise in case-control genetic association studies if there is an association between survival and genetic variants under study. It is difficult to detect and adjust for the bias if no genetic data are available from deceased cases. Here, we propose to incorporate genotype data from family members (such as offspring, spouses, or parents) of deceased cases into retrospective maximum likelihood analysis. Our method permits unbiased estimation of genotype association parameters. This method faces an identifiability issue under a co-dominant model for both penetrance and survival given disease, so model simplifications are required. We derive closed-form maximum likelihood estimates for association parameters under the widely used log-additive and dominant association models. Our proposed method can improve validity and study power by incorporating familial genotype data from deceased cases, and we provide simulation results and a data example to demonstrate achievable improvements.