Introduction of the IBD information into the weighted pairwise correlation method for linkage analysis

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Abstract
The Weighted Pairwise Correlation (WPC) approach is a non-parametric method of linkage analysis that allows analysis of any kind of phenotypes (quantitative, binary, binary with age of onset) and to consider all pairs of relatives in a pedigree. The principle of this method is to test whether two relatives having close phenotypes also resemble at the marker locus more than expected under the null hypothesis of no linkage. So far, this marker resemblance was estimated by the proportion of alleles shared Identical By State (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 relatives having the same reference couple using individual genotypic vectors derived from this couple. This reconstruction of the IBD information is performed rapidly even in large pedigrees. Simulation studies conducted under various genetic models demonstrate that the use of IBD instead of IBS information leads to a large increase of power, especially in the situation of poorly informative markers.