Linkage detection tests under heterogeneity.
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.
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06510.
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Risch
D003627:Data Interpretation, Statistical; D004812:Epidemiologic Methods; D008040:Genetic Linkage; D006579:Heterozygote; D006801:Humans; D008126:Lod Score; D008433:Mathematics