Robust genetic linkage analysis based on a score test of homogeneity: the weighted pairwise correlation statistic

Abstract

In testing genetic linkage using large or complex pedigrees, robust methods may be preferred to the Lod-score method. The affected-pedigree-member method is robust but does not use the information available in nonaffected subjects, which results in a loss of power. We propose a new test of genetic linkage based on a score test of homogeneity derived from a random effect model. The statistic is simple and uses only pairs of subjects. In contrast with the affected-pedigree-method, it uses all the available pairs and does not depend on the marker alleles frequencies. A rank version of this weighted pairwise correlation statistic is proposed, its exact first and second moment derived. We show that for age-dependent diseases, it provides a simple nonparametric test.