The quantitative trait linkage disequilibrium test

A more powerful alternative to the quantitative transmission disequilibrium test for use in the absence of population stratification

Lorena M. Havill, Thomas D. Dyer, Dawn K. Richardson, Michael C. Mahaney, John Blangero

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Linkage analysis based on identity-by-descent allele-sharing can be used to identify a chromosomal region harboring a quantitative trait locus (QTL), but lacks the resolution required for gene identification. Consequently, linkage disequilibrium (association) analysis is often employed for fine-mapping. Variance-components based combined linkage and association analysis for quantitative traits in sib pairs, in which association is modeled as a mean effect and linkage is modeled in the covariance structure has been extended to general pedigrees (quantitative transmission disequilibrium test, QTDT). The QTDT approach accommodates data not only from parents and siblings, but also from all available relatives. QTDT is also robust to population stratification. However, when population stratification is absent, it is possible to utilize even more information, namely the additional information contained in the founder genotypes. In this paper, we introduce a simple modification of the allelic transmission scoring method used in the QTDT that results in a more powerful test of linkage disequilibrium, but is only applicable in the absence of population stratification. This test, the quantitative trait linkage disequilibrium (QTLD) test, has been incorporated into a new procedure in the statistical genetics computer package SOLAR. We apply this procedure in a linkage/association analysis of an electrophysiological measurement previously shown to be related to alcoholism. We also demonstrate by simulation the increase in power obtained with the QTLD test, relative to the QTDT, when a true association exists between a marker and a QTL.

Original languageEnglish (US)
Article numberS91
JournalBMC Genetics
Volume6
Issue numberSUPPL.1
DOIs
StatePublished - Dec 30 2005
Externally publishedYes

Fingerprint

Linkage Disequilibrium
Quantitative Trait Loci
Population
Pedigree
Alcoholism
Research Design
Alleles
Genotype
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

The quantitative trait linkage disequilibrium test : A more powerful alternative to the quantitative transmission disequilibrium test for use in the absence of population stratification. / Havill, Lorena M.; Dyer, Thomas D.; Richardson, Dawn K.; Mahaney, Michael C.; Blangero, John.

In: BMC Genetics, Vol. 6, No. SUPPL.1, S91, 30.12.2005.

Research output: Contribution to journalArticle

Havill, Lorena M. ; Dyer, Thomas D. ; Richardson, Dawn K. ; Mahaney, Michael C. ; Blangero, John. / The quantitative trait linkage disequilibrium test : A more powerful alternative to the quantitative transmission disequilibrium test for use in the absence of population stratification. In: BMC Genetics. 2005 ; Vol. 6, No. SUPPL.1.
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