Adaptive Transmission Disequilibrium Test for Family Trio Design

Yuan Min, Tian Xin, Zheng Gang and Yang Yaning
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Yuan Min: University of Science and Technology of China
Tian Xin: National Heart, Lung and Blood Institute
Zheng Gang: National Heart, Lung and Blood Institute
Yang Yaning: University of Science and Technology of China

Statistical Applications in Genetics and Molecular Biology, 2009, vol. 8, issue 1, 22

Abstract: The transmission disequilibrium test (TDT) is a standard method to detect association using family trio design. It is optimal for an additive genetic model. Other TDT-type tests optimal for recessive and dominant models have also been developed. Association tests using family data, including the TDT-type statistics, have been unified to a class of more comprehensive and flexable family-based association tests (FBAT). TDT-type tests have high efficiency when the genetic model is known or correctly specified, but may lose power if the model is mis-specified. Hence tests that are robust to genetic model mis-specification yet efficient are preferred. Constrained likelihood ratio test (CLRT) and MAX-type test have been shown to be efficiency robust. In this paper we propose a new efficiency robust procedure, referred to as adaptive TDT (aTDT). It uses the Hardy-Weinberg disequilibrium coefficient to identify the potential genetic model underlying the data and then applies the TDT-type test (or FBAT for general applications) corresponding to the selected model. Simulation demonstrates that aTDT is efficiency robust to model mis-specifications and generally outperforms the MAX test and CLRT in terms of power. We also show that aTDT has power close to, but much more robust, than the optimal TDT-type test based on a single genetic model. Applications to real and simulated data from Genetic Analysis Workshop (GAW) illustrate the use of our adaptive TDT.

Keywords: adaptive TDT; conditional power; efficiency robustness; genetic model selection; Hardy-Weinberg disequilibrium; MAX-type tests; TDT-type tests; FBAT; constrained likelihood ratio test (search for similar items in EconPapers)
Date: 2009
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DOI: 10.2202/1544-6115.1451

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