Adaptive transmission disequilibrium test for family trio design.
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.
Yuan
Min
M
University of Science and Technology of China. myuan@mail.ustc.edu.cn
Tian
Xin
X
Zheng
Gang
G
Yang
Yaning
Y
D001172:Arthritis, Rheumatoid / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D003198:Computer Simulation; D005190:Family; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics*; D008126:Lod Score; D008957:Models, Genetic; D015233:Models, Statistical; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012107:Research Design / Q000706:statistics & numerical data*
D006684:HLA-DR Antigens