SNP-Based Linkage Analysis in Extended Pedigrees: Comparison between Two Alternative Approaches

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 es...

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Bibliographic Details
Published in:Human heredity 2014-01, Vol.78 (1), p.27-37
Main Authors: Saint-Pierre, Aude, D’Elia, Yuri, Ciullo, Marina, Pramstaller, Peter P., Pattaro, Cristian
Format: Article
Language:English
Subjects:
Chromosome Mapping - methods
Computer Simulation
Female
Genetic Linkage
Genetic markers
Genetics, Population - methods
Genotype
Heredity
Humans
Lod Score
Male
Models, Genetic
Original Paper
Pedigree
Polymorphism
Polymorphism, Single Nucleotide
Quantitative Trait Loci - genetics
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Summary: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.
ISSN:0001-5652
1423-0062
DOI:10.1159/000360623