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 samp les. All analyses were conducted without knowledge of the generating models . To assess power and consistency of results within and between samples, an alyses were repeated in all 25 replicates combined and in each replicate. W ith the exception of sample-specific findings for locus D, power was genera lly low to detect linkage in a genome scan or to confirm linkages detected by allele sharing in affected relatives, due to lack of linkage disequilibr ium. We proposed likelihood ratio and Wald tests to detect heterogeneity am ong samples in disease-marker associations. Pooling data across heterogeneo us populations may not improve power of the TDT method. ((C)) 1999 Wiley-Li ss, Inc.