Power of the admixture test to detect genetic heterogeneity

Several dominant genetic diseases which appear to be homogeneous are the expression of genetic mutations at several loci. The power to detect linkage by likelihood methods is diminished for heterogeneous, as compared to genetically homogeneous, disorders. Using a simulation approach and two pedigrees typical of those available for the study of a dominant disease (with expected lod scores of 0.43 and 1.00 at theta = 0.05 and PIC = .59), I have evaluated the power to detect genetic heterogeneity by using the admixture test. Linkage power was determined by varying the number of families available for study, the recombination fraction (theta), the informativity of the hypothetical marker, and the proportion of linked families, alpha. For moderate and small values of alpha it is feasible to detect genetic heterogeneity once linkage has been established; rarely will it be possible to detect linkage and heterogeneity simultaneously given a limited number of small or moderate pedigrees.