Unlike the population-based studies, family-based studies are resistant to type I errors arising from population stratification. The family-based Transmission/Disequilibrium Test (TDT) measures the over-transmission of an allele from heterozygous parents to their affected offspring, in which the non-transmitted parental alleles serve, in effect, as a control group. Therefore the TDT is a robust test of association in the presence of geographical or ethnical impact from the population [17]. In the original TDT [18], a parent-proband trio is considered as a basic unit, in which a proband is the first affected family member who seeks medical attention for a genetic disorder. Assuming complete genotype information for a two allele marker locus in each trio, the TDT compares the number of heterozygous parents who transmit either allele to the affected offspring. The TDT can be constructed through a 2 by 2 table ( Table 1 ). Under the null hypothesis of no associaton, the proportions & are tested against (0.5, 0.5) using a binomial (asymptotically chi-square) test with one degree of freedom:(1)
