Power of the TDT to detect association: effect of linkage disequilibrium between genetic markers and an unobserved disease mutation

The transmission disequilibrium test (TDT) is widely used to test for association in families. Many previous papers have shown sample size calculations where the true disease mutation is tested. When a neighbouring marker is used in place of the mutation, the power to detect association depends on the linkage disequilibrium between the loci. A difference in frequency between the mutation and the tested allele, or a reduction in linkage disequilibrium will substantially increase the required sample size. If a study design includes reasonable assumptions regarding linkage disequilibrium, using the TDT with anonymous nonfunctional markers may not be feasible.