title: Power comparisons between the TDT and two likelihood-based methods.
abstract: We compare the statistical power of the transmission disequilibrium test (TDT) with that of two likelihood-based linkage tests, the classical LOD score and a modified LOD score in which a linkage disequilibrium (LD) parameter is incorporated into the likelihood (LD-LOD). We hypothesize that, when LD is present, the LD-LOD will have the greatest power of the three tests because the TDT breaks a multiplex pedigree into triads, and the LOD score has previously been shown to have lower power when LD is present but not accounted for. We test this hypothesis using a simulation study in which we generate affected sib-pair (ASP) pedigrees under a range of genetic models, varying the genotypic relative risk (GRR) from 6 to 16. Because the likelihood-based tests require that a genetic model be specified, we compare the tests under two scenarios. First, we assume the true genetic model in the analysis, and second, we compare the tests when the LD-LOD (LOD) is maximized over two wrong genetic models. For the generating models we considered, we find that the LD-LOD has greater power than the TDT even when the genetic models is mis-specified and the results corrected for multiple tests. Extreme differences occur under the multiplicative and dominant models, for which the difference in power is as high as 40% at complete LD. The LOD score provides the lowest power in the presence of LD for the range of GRR considered here.
authors.affiliation: Department of Biostatistics, University of Iowa, Iowa City, Iowa, USA. slager@mayo.edu
authors.forename: S L
authors.initials: SL
authors.lastname: Slager
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.forename: V J
authors.initials: VJ
authors.lastname: Vieland
mesh_terms: D000328:Adult; D000483:Alleles; D002648:Child; D005190:Family; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D005821:Genetic Techniques; D005826:Genetics, Medical; D006801:Humans; D016013:Likelihood Functions; D015810:Linkage Disequilibrium; D008126:Lod Score; D008297:Male; D013223:Statistics as Topic
chemical_list: D005819:Genetic Markers