Linkage detection tests under heterogeneity

Abstract

A two-parameter (admixture) test (Lod₂) for the detection of linkage which allows for heterogeneity is described. Lod score values for this test which lead to comparable type 1 error probabilities as the conventional (homogeneous) single-parameter lod score test (Lod₁) are derived. For example, a Lod₂ value of 3.70 corresponds to the conventional lod score (Lod₁) value of 3.0. In terms of power to detect linkage, the Lod₂ test is advantageous only for moderate to large pedigrees (autosomal dominant inheritance with high penetrance) and when the proportion of linked families is low (less than 40%). Otherwise, there appears to be no serious disadvantage in using the conventional Lod₁ test when heterogeneity is present.