Comparison of multivariate tests for genetic linkage

Objectives: Multivariate tests for linkage can provide im proved power over univariate tests but the type I error rates and comparative power of commo nly used methods have not previously been compared. Here we studied the beh avior of bivariate formulations of the variance component (VC) and Haseman- Elston (H-E) approaches. Methods: We compared through simulation studies th e bivariate H-E test with the unconstrained bivariate VC approach and with a VC approach in which the major-gene correlation is constrained to +/-1. W e also compared these methods to univariate methods, Results: Bivariate app roaches are more powerful than univariate analyses unless the traits are ve ry highly positively correlated. The power of the bivariate H-E test was le ss than the VC procedures. The constrained test was often less powerful tha n the unconstrained test. The empirical distributions of the bivariate H-E test and the unconstrained bivariate VC test conformed with asymptotic dist ributions for samples of 100 or more sibships of size 4, Conclusions: The u nconstrained VC test is valuable for testing for preliminary linkages using multivariate phenotypes. The bivariate H-E test was less powerful than the bivariate VC tests. Copyright (C) 2001 S. Karger AG, Basel.