Power comparisons between the TDT and two likelihood-based methods

S. L. Slager, Jian Huang, V. J. Vieland

Research output: Journal article publicationJournal articleAcademic researchpeer-review

5 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)192-209
Number of pages18
JournalGenetic Epidemiology
Volume20
Issue number2
DOIs
Publication statusPublished - 8 Feb 2001
Externally publishedYes

Keywords

  • Association tests
  • Genotypic relative risks
  • Linkage tests
  • LOD score

ASJC Scopus subject areas

  • Epidemiology
  • Genetics(clinical)

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