Evaluation of methodology for the analysis of 'time-to-event' data in pharmacogenomic genome-wide association studies

Abstract

Aim: To evaluate the power to detect associations between SNPs and time-to-event outcomes across a range of pharmacogenomic study designs while comparing alternative regression approaches. Materials & methods: Simulations were conducted to compare Cox proportional hazards modeling accounting for censoring and logistic regression modeling of a dichotomized outcome at the end of the study. Results: The Cox proportional hazards model was demonstrated to be more powerful than the logistic regression analysis. The difference in power between the approaches was highly dependent on the rate of censoring. Conclusion: Initial evaluation of single-nucleotide polymorphism association signals using computationally efficient software with dichotomized outcomes provides an effective screening tool for some design scenarios, and thus has important implications for the development of analytical protocols in pharmacogenomic studies.