SNP-based linkage analysis in extended pedigrees: comparison between two alternative approaches.

ABSTRACT

BACKGROUND: Linkage analysis on extended pedigrees is often challenged by the high computational demand of exact identity-by-descent (IBD) matrix reconstruction. When such an analysis becomes not feasible, two alternative solutions are contrasted a full pedigree analysis based on approximate IBD estimation versus a pedigree splitting followed by exact IBD estimation. A multiple splitting (MS) approach, which combines linkage results across different splitting configurations, has been proposed to increase the power of single-split solutions. METHODS: To assess whether MS can achieve a comparable power to a full pedigree analysis, we compared the power of linkage on a very large pedigree in both simulated and real-case scenarios, using variance components linkage analysis of a dense SNP array. RESULTS: Our results confirm that the power to detect linkage is affected by the pedigree size. The MS approach showed higher power than the single-split analysis, but it was substantially less powerful than the full pedigree approach in both scenarios, at any level of significance and variance explained by a quantitative trait locus. CONCLUSION: The MS approach should always be preferred to analyses based on a single split but, when adequate computational resources are available, a full pedigree analysis is better than the MS analysis. Rather than focusing on how to best split a pedigree, it might be more valuable to identify computational solutions that can make the IBD estimation of dense-marker maps practically feasible, thus allowing a full pedigree analysis.