JSM 2011 Online Program

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Abstract Details

Activity Number: 357
Type: Contributed
Date/Time: Tuesday, August 2, 2011 : 10:30 AM to 12:20 PM
Sponsor: Section on Statistics in Epidemiology
Abstract - #302794
Title: Unified Analysis of Secondary Phenotypes in Case-Control Association Studies
Author(s): Arpita Ghosh*+ and Fei Zou and Fred Andrew Wright
Companies: National Cancer Institute and The University of North Carolina at Chapel Hill and The University of North Carolina
Address: , , ,
Keywords: case-control association study ; secondary phenotype ; secondary analysis ; retrospective likelihood ; profile likelihood ; pseudo likelihood
Abstract:

It has been repeatedly shown that in case-control sampled association studies, analysis of the secondary phenotypes ignoring the sampling scheme can produce highly biased risk estimates. Although a number of approaches have been proposed to properly analyze secondary phenotypes, these approaches often fail to reproduce the marginal logistic model typically assumed for the original case-control phenotype. In addition, handling covariates, especially continuous ones, in a flexible manner remains challenging. We provide a general retrospective likelihood framework to perform association testing for both binary and continuous secondary phenotypes while respecting desired marginal models and allowing for interaction between the genetic variant and the secondary phenotype on primary disease risk. We use a profile likelihood technique to handle the covariates and provide an easy algorithm for deriving the estimator. We also present an alternative approach to handling the covariates based on the pseudo likelihood method. We describe extensive simulations to evaluate the performance of the profile likelihood method in comparison with the pseudo likelihood and other competing methods.


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