An empirical test of the significance of an observed quantitative trait locus effect that preserves additive genetic variation

We propose a constrained permutation test that assesses the significance of an observed quantitative trait locus effect against a background of geneti c and environmental variation. Permutations of phenotypes are not selected at random, but rather are chosen in a manner that attempts to maintain the additive genetic variability in phenotypes. Such a constraint maintains the nonindependence among observations under the null hypothesis of no linkage . The empirical distribution of the lod scores calculated using permuted ph enotypes is compared to that obtained using phenotypes simulated from the a ssumed underlying multivariate normal model. We make comparisons of univari ate analyses for both a quantitative phenotype that appears consistent with a multivariate normal model and a quantitative phenotype containing pronou nced outliers. An example of a bivariate analysis is also presented. (C) 19 99 Wiley-Liss, Inc.