title: Replication of linkage studies of complex traits: an examination of variation in location estimates.
abstract: In linkage studies, independent replication of positive findings is crucial in order to distinguish between true positives and false positives. Recently, the following question has arisen in linkage studies of complex traits: at what distance do we reject the hypothesis that two location estimates in a genomic region represent the same gene? Here we attempt to address this question. Sampling distributions for location estimates were constructed by computer simulation. The conditions for simulation were chosen to reflect features of "typical" complex traits, including incomplete penetrance, phenocopies, and genetic heterogeneity. Our findings, which bear on what is considered a replication in linkage studies of complex traits, suggest that, even with relatively large numbers of multiplex families, chance variation in the location estimate is substantial. In addition, we report evidence that, for the conditions studied here, the standard error of a location estimate is a function of the magnitude of the expected LOD score.
authors.affiliation: Department of Human Genetics, Virginia Institute of Psychiatric and Behavioral Genetics, Medical College of Virginia of Virginia Commonwealth University, Richmond, VA 23298-0126, USA.
authors.forename: S B
authors.initials: SB
authors.lastname: Roberts
authors.forename: C J
authors.initials: CJ
authors.lastname: MacLean
authors.forename: M C
authors.initials: MC
authors.lastname: Neale
authors.forename: L J
authors.initials: LJ
authors.lastname: Eaves
authors.forename: K S
authors.initials: KS
authors.lastname: Kendler
mesh_terms: D002874:Chromosome Mapping / Q000379:methods*; D002877:Chromosomes, Human / Q000235:genetics; D003198:Computer Simulation; D005787:Gene Frequency; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D018740:Genetic Heterogeneity; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016013:Likelihood Functions; D008126:Lod Score; D020412:Multifactorial Inheritance / Q000235:genetics*; D019683:Penetrance; D010641:Phenotype; D018401:Sample Size; D012680:Sensitivity and Specificity; D016008:Statistical Distributions
chemical_list: D005819:Genetic Markers