The original transmission disequilibrium test (TDT), was introduced
to test for linkage between
a marker and a disease-susceptibility locus (Spielman et al. 1993).
Allison (1997) extended the TDT
procedure to quantitative traits. Allison's test, however, is restrictive
in that it requires family trios
consisting of one heterozygous parent, one homozygous parent and one child,
and considers only the
situation where the marker locus is analogous to the quantitative trait
locus itself. In this paper, we
propose, investigate and apply a general TDT for quantitative traits that
permits more than one
child per family, does not require only one parent to be heterozygous,
and allows for the fact that
the various alleles at the marker and trait loci may be at varying degree
of linkage disequilibrium.
We also show that this TDT for quantitative traits is still a valid test
of linkage in the presence of
population substructure. To provide guidelines for study design, we develop
analytic formulae for
calculation of the power of the TDT for mapping quantitative trait loci
and investigate the impact
of various factors on the power. Power calculations show that the proposed
TDT for quantitative
traits is more powerful than Allison's basic test statistic and the
extreme discordant sib pair linkage
method. The proposed TDT statistic for quantitative traits is applied to
systolic blood pressure
variation in the Rochester Family Heart Study using an extremely discordant
sibling pair design.