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.