title: Replication of linkage to quantitative trait loci: variation in location and magnitude of the lod score.
abstract: Replication of linkage signals from independent samples is considered an important step toward verifying the significance of linkage signals in studies of complex traits. The purpose of this empirical investigation was to examine the variability in the precision of localizing a quantitative trait locus (QTL) by analyzing multiple replicates of a simulated data set with the use of variance components-based methods. Specifically, we evaluated across replicates the variation in both the magnitude and the location of the peak lod scores. We analyzed QTLs whose effects accounted for 10-37% of the phenotypic variance in the quantitative traits. Our analyses revealed that the precision of QTL localization was directly related to the magnitude of the QTL effect. For a QTL with effect accounting for > 20% of total phenotypic variation, > 90% of the linkage peaks fall within 10 cM from the true gene location. We found no evidence that, for a given magnitude of the lod score, the presence of interaction influenced the precision of QTL localization.
authors.affiliation: Department of Genetics, Southwest Foundation for Biomedical Research, P.O. Box 760549, San Antonio, TX 78245, USA.
authors.forename: W C
authors.initials: WC
authors.lastname: Hsueh
authors.forename: H H
authors.initials: HH
authors.lastname: Göring
authors.forename: J
authors.initials: J
authors.lastname: Blangero
authors.forename: B D
authors.initials: BD
authors.lastname: Mitchell
mesh_terms: D002874:Chromosome Mapping / Q000706:statistics & numerical data*; D014644:Genetic Variation; D006801:Humans; D008126:Lod Score; D008957:Models, Genetic; D010641:Phenotype; D019655:Quantitative Trait, Heritable