Comparison of family-based association tests in chromosome regions selected by linkage-based confidence intervals

Juan Pablo Lewinger, Sophia S F Lee, Joanna M Biernacka, Long Yang Wu, Haijiang Steven Shi, Shelley B. Bull

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Abstract

We use the Genetic Analysis Workshop 14 simulated data to explore the effectiveness of a two-stage strategy for mapping complex disease loci consisting of an initial genome scan with confidence interval construction for gene location, followed by fine mapping with family-based tests of association on a dense set of single-nucleotide polymorphisms. We considered four types of intervals: the 1-LOD interval, a basic percentile bootstrap confidence interval based on the position of the maximum Zlr score, and asymptotic and bootstrap confidence intervals based on a generalized estimating equations method. For fine mapping we considered two family-based tests of association: a test based on a likelihood ratio statistic and a transmission-disequilibrium-type test implemented in the software FBAT. In two of the simulation replicates, we found that the bootstrap confidence intervals based on the peak Zlr and the 1-LOD support interval always contained the true disease loci and that the likelihood ratio test provided further strong confirmatory evidence of the presence of disease loci in these regions.

Original languageEnglish (US)
Article numberS62
JournalBMC Genetics
Volume6
Issue numberSUPPL.1
DOIs
StatePublished - Dec 30 2005
Externally publishedYes

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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