Statistical tests for detection of misspecified relationships by use of genome-screen data.
Misspecified relationships can have serious consequences for linkage studies, resulting in either reduced power or false-positive evidence for linkage. If some individuals in the pedigree are untyped, then Mendelian errors may not be observed. Previous approaches to detection of misspecified relationships by use of genotype data were developed for sib and half-sib pairs. We extend the likelihood calculations of Göring and Ott and Boehnke and Cox to more-general relative pairs, for which identity-by-descent (IBD) status is no longer a Markov chain, and we propose a likelihood-ratio test. We also extend the identity-by-state (IBS)-based test of Ehm and Wagner to nonsib relative pairs. The likelihood-ratio test has high power, but its drawbacks include the need to construct and apply a separate Markov chain for each possible alternative relationship and the need for simulation to assess significance. The IBS-based test is simpler but has lower power. We propose two new test statistics-conditional expected IBD (EIBD) and adjusted IBS (AIBS)-designed to retain the simplicity of IBS while increasing power by taking into account chance sharing. In simulations, the power of EIBD is generally close to that of the likelihood-ratio test. The power of AIBS is higher than that of IBS, in all cases considered. We suggest a strategy of initial screening by use of EIBD and AIBS, followed by application of the likelihood-ratio test to only a subset of relative pairs, identified by use of EIBD and AIBS. We apply the methods to a Genetic Analysis Workshop 11 data set from the Collaborative Study on the Genetics of Alcoholism.
McPeek
M S
MS
Department of Statistics, University of Chicago, Chicago, IL, 60637, USA. mcpeek@galton.uchicago.edu
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D000437:Alcoholism / Q000235:genetics; D000483:Alleles; D002874:Chromosome Mapping / Q000379:methods* / Q000706:statistics & numerical data; D003198:Computer Simulation; D003241:Consanguinity; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005820:Genetic Testing; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D008390:Markov Chains; D016555:Matched-Pair Analysis; D018895:Microsatellite Repeats / Q000235:genetics; D008957:Models, Genetic; D009679:Nuclear Family; D010375:Pedigree