Power comparisons between the TDT and two likelihood-based methods

We compare the statistical power of the transmission disequilibrium test (T DT) with that of two Likelihood-based linkage tests, the classical LOD scor e and a modified LOD score in which a linkage disequilibrium (LD) parameter is incorporated into the likelihood (LD-LOD). We hypothesize that, when LD is present, the LD-LOD will have the greatest power of the three tests bec ause the TDT breaks a multiplex pedigree into triads, and the LOD score has previously been shown to have lower power when LD is present but not accou nted for. We test this hypothesis using a simulation study in which we gene rate affected sib-pair (ASP) pedigrees under a range of genetic models, var ying the genotypic relative risk (GRR) from 6 to 16. Because the Likelihood -based tests require that a genetic model be specified, we compare the test s under two scenarios. First, we assume the true genetic model in the analy sis, and second, we compare the tests when the LD-LOD (LOD) is maximized ov er two wrong genetic models. For the generating models we considered, we fi nd that the LD-LOD has greater power than the TDT even when the genetic mod els is mis-specified and the results corrected for multiple tests. Extreme differences occur under the multiplicative and dominant models, for which t he difference in power is as high as 40% at complete LD. The LOD score prov ides the lowest power in the presence of LD for the range of GRR considered here. (C) 2001 Wiley-Liss, Inc.