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.

Submitted: February 19, 2009 · Accepted: June 17, 2009 · Published: June 23, 2009

Recommended Citation

Yuan, Min; Tian, Xin; Zheng, Gang; and Yang, Yaning (2009) "Adaptive Transmission Disequilibrium Test for Family Trio Design," Statistical Applications in Genetics and Molecular Biology: Vol. 8 : Iss. 1, Article 30.
DOI: 10.2202/1544-6115.1451
Available at: http://www.bepress.com/sagmb/vol8/iss1/art30