The Cluster Variation Method for Efficient Linkage Analysis on Extended Pedigrees

Background: Computing exact multipoint LOD scores for extended pedigrees rapidly becomes infeasible as the number of markers and untyped individuals increase. When markers are excluded from the computation, significant power may be lost. Therefore accurate approximate methods which take into account all markers are desirable. Methods: We present a novel method for efficient estimation of LOD scores on extended pedigrees. Our approach is based on the Cluster Variation Method, which deterministically estimates likelihoods by performing exact computations on tractable subsets of variables (clusters) of a Bayesian network. First a distribution over inheritances on the marker loci is approximated with the Cluster Variation Method. Then this distribution is used to estimate the LOD score for each location of the trait locus. Results: First we demonstrate that significant power may be lost if markers are ignored in the multi-point analysis. On a set of pedigrees where exact computation is po...

• Type: Journal
• Year: 2006
• Where: BMCBI
• Authors: Cornelis A. Albers, Martijn A. R. Leisink, Hilbert J. Kappen
• Keywords: BMCBI 2006, Cluster Variation Method, Lod Scores, Markers