Disease-marker associations: power and heterogeneity in independent population samples.
We applied generalized transmission disequilibrium testing (TDT) models in combined replicates 1 through 5 from each of four simulated population samples. All analyses were conducted without knowledge of the generating models. To assess power and consistency of results within and between samples, analyses were repeated in all 25 replicates combined and in each replicate. With the exception of sample-specific findings for locus D, power was generally low to detect linkage in a genome scan or to confirm linkages detected by allele sharing in affected relatives, due to lack of linkage disequilibrium. We proposed likelihood ratio and Wald tests to detect heterogeneity among samples in disease-marker associations. Pooling data across heterogeneous populations may not improve power of the TDT method.