The power of the transmission disequilibrium test (TDT) with both case–parent and control–parent trios

Abstract

The transmission disequilibrium test (TDT) customarily uses affected children and their parents (often case–parent trios, TDTD). Control–parent trios are necessary to guard against spurious significant results due to segregation distortion but are not generally utilized in the identification of disease susceptibility loci (DSL). Controls are often easy to recruit and the TDT can easily be extended to include control–parent trios into the analyses with unrelated case–parent trios. We present an extension of the TDT (TDTDC) that incorporates unrelated cases and controls and their parents into a single analysis. We develop a simple and accurate analytical method for computing the statistical power of various TDT (e.g. the TDTD, TDTDC, TDTDC and TDTC that employ control–parent trios only) under any genetic model. We investigated the power of these TDT, and particularly compared the relative power of the TDTD and TDTDC. We found that the TDTDC is almost always more powerful than the TDTC and TDTD. The relative power of the TDTDC and TDTD depends largely upon a number of parameters identified in the study. This study provides a basis for efficient use of control–parent trios in DSL identification.