Transmission Disequilibrium Test (TDT)-based methods have been advocated by several authors
for testing that a marker-phenotype association is actually due to linkage and not to uncontrolled
stratification. As a pre-requisite of TDT-type methods is the presence of an association between
marker and phenotype, one may wish to first investigate the association using a classical association
study, and then to check by a TDT approach whether this association is actually due to linkage. We
propose an estimating equation (EE) procedure, to compute analytically the minimum sample size
of sibship data required to detect the association between a marker and a quantitative phenotype,
and that required to confirm it by two TDT methods. We show that, when the marker allele
frequency is low or high, the number of informative sibs needed in TDT-type methods can be lower
than the number required in an association analysis, and even more so when the familial clustering
is strong. However, in all cases, the number of sibs that need to be sampled to get the appropriate
number of informative sibs for analysis is always larger for TDT methods than for an association
study. In a phenotype-first strategy, this number may be critical when investigating costly
phenotypes.