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||Retrospective versus prospective score tests for genetic association with case-control data.
||Liu Y, Li P, Song L, Yu K, Qin J
||Since the seminal work of Prentice and Pyke, the prospective logistic likelihood has become the standard method of analysis for retrospectively collected case-control data, in particular for testing the association between a single genetic marker and a disease outcome in genetic case-control studies. In the study of multiple genetic markers with relatively small effects, especially those with rare variants, various aggregated approaches based on the same prospective likelihood have been developed to integrate subtle association evidence among all the markers considered. Many of the commonly used tests are derived from the prospective likelihood under a common-random-effect assumption, which assumes a common random effect for all subjects. We develop the locally most powerful aggregation test based on the retrospective likelihood under an independent-random-effect assumption, which allows the genetic effect to vary among subjects. In contrast to the fact that disease prevalence information cannot be used to improve efficiency for the estimation of odds ratio parameters in logistic regression models, we show that it can be utilized to enhance the testing power in genetic association studies. Extensive simulations demonstrate the advantages of the proposed method over the existing ones. A real genome-wide association study is analyzed for illustration.