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Testing the robustness of the likelihood-ratio test in a variance-component quantitative-trait loci-mapping procedure

Academic Article
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Overview

authors

  • Allison, D. B.
  • Neale, M. C.
  • Zannolli, R.
  • Schork, Nicholas
  • Amos, C. I.
  • Blangero, J.

publication date

  • August 1999

journal

  • American Journal of Human Genetics  Journal

abstract

  • Detection of linkage to genes for quantitative traits remains a challenging task. Recently, variance components (VC) techniques have emerged as among the more powerful of available methods. As often implemented, such techniques require assumptions about the phenotypic distribution. Usually, multivariate normality is assumed. However, several factors may lead to markedly nonnormal phenotypic data, including (a) the presence of a major gene (not necessarily linked to the markers under study), (b) some types of gene x environment interaction, (c) use of a dichotomous phenotype (i.e., affected vs. unaffected), (d) nonnormality of the population within-genotype (residual) distribution, and (e) selective (extreme) sampling. Using simulation, we have investigated, for sib-pair studies, the robustness of the likelihood-ratio test for a VC quantitative-trait locus-detection procedure to violations of normality that are due to these factors. Results showed (a) that some types of nonnormality, such as leptokurtosis, produced type I error rates in excess of the nominal, or alpha, levels whereas others did not; and (b) that the degree of type I error-rate inflation appears to be directly related to the residual sibling correlation. Potential solutions to this problem are discussed. Investigators contemplating use of this VC procedure are encouraged to provide evidence that their trait data are normally distributed, to employ a procedure that allows for nonnormal data, or to consider implementation of permutation tests.

subject areas

  • Analysis of Variance
  • Chromosome Mapping
  • Computer Simulation
  • Genetic Linkage
  • Humans
  • Likelihood Functions
  • Matched-Pair Analysis
  • Nuclear Family
  • Phenotype
  • Quantitative Trait, Heritable
  • Reproducibility of Results
  • Sample Size
  • Software
  • Statistical Distributions
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Identity

PubMed Central ID

  • PMC1377951

International Standard Serial Number (ISSN)

  • 0002-9297

Digital Object Identifier (DOI)

  • 10.1086/302487

PubMed ID

  • 10417295
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Additional Document Info

start page

  • 531

end page

  • 544

volume

  • 65

issue

  • 2

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