Introduction of the IBD information into the Weighted Pairwise Correlationmethod for linkage analysis

The Weighted Pairwise Correlation (WPC) approach is a non-parametric method of linkage analysis that allows analysis of any kind of phenotypes (quanti tative, binary, binary with age of onset) and to consider all pairs of rela tives in a pedigree. The principle of this method is to test whether two re latives having close phenotypes also resemble at the marker locus more than expected under the null hypothesis of no linkage. So far, this marker rese mblance was estimated by the proportion of alleles shared Identical By Stat e (IBS) by the two relatives. Here, we propose a method to incorporate the Identical By Descent (IBD) information into the WPC approach. For any kind of relative pairs, the computation of the proportion of alleles shared IBD is based on the identification of the closest couple of ancestors, denoted as the reference couple. The IBD information is obtained for pairs of relat ives having the same reference couple using individual genotypic vectors de rived from this couple. This reconstruction of the IBD information is perfo rmed rapidly even in large pedigrees. Simulation studies conducted under va rious genetic models demonstrate that the use of IBD instead of IBS informa tion leads to a large increase of power, especially in the situation of poo rly informative markers. Genet. Epidemiol. 17:35-50, 1999. (C) 1999 Wiley-L iss, Inc.