A Transmission/Disequilibrium Test That Allows for Genotyping Errors in the Analysis of Single-Nucleotide Polymorphism Data

The present study assesses the effects of genotyping errors on the type I error rate of a particular transmission/disequilibrium test (TDTstd), which assumes that data are errorless, and introduces a new transmission/disequilibrium test (TDTae) that allows for random genotyping errors. We evaluate the type I error rate and power of the TDTae under a variety of simulations and perform a power comparison between the TDTstd and the TDTae, for errorless data. Both the TDTstd and the TDTae statistics are computed as two times a log-likelihood difference, and both are asymptotically distributed as χ2 with 1 df. Genotype data for trios are simulated under a null hypothesis and under an alternative (power) hypothesis. For each simulation, errors are introduced randomly via a computer algorithm with different probabilities (called “allelic error rates”). The TDTstd statistic is computed on all trios that show Mendelian consistency, whereas the TDTae statistic is computed on all trios. The results indicate that TDTstd shows a significant increase in type I error when applied to data in which inconsistent trios are removed. This type I error increases both with an increase in sample size and with an increase in the allelic error rates. TDTae always maintains correct type I error rates for the simulations considered. Factors affecting the power of the TDTae are discussed. Finally, the power of TDTstd is at least that of TDTae for simulations with errorless data. Because data are rarely error free, we recommend that researchers use methods, such as the TDTae, that allow for errors in genotype data