An empirical test of the significance of an observed quantitative trait locus effect that preserves additive genetic variation

We propose a constrained permutation test that assesses the significance of an observed quantitative trait locus effect against a background of genetic and environmental variation. Permutations of phenotypes are not selected at random, but rather are chosen in a manner that attempts to maintain the...

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Bibliographic Details
Published in:Genetic epidemiology 1999, Vol.17 (S1), p.S169-S173
Main Authors: Iturria, Stephen J., Williams, Jeff T., Almasy, Laura, Dyer, Thomas D., Blangero, John
Format: Article
Language:English
Subjects:
Alcoholism - enzymology
Alcoholism - genetics
Alcoholism - physiopathology
Chi-Square Distribution
Event-Related Potentials, P300 - genetics
Genetic Testing
Genetic Variation
Humans
Lod Score
Monoamine Oxidase - genetics
Multivariate Analysis
permutation test
power
quantitative trait locus
Quantitative Trait, Heritable
statistical genetics
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Summary:We propose a constrained permutation test that assesses the significance of an observed quantitative trait locus effect against a background of genetic and environmental variation. Permutations of phenotypes are not selected at random, but rather are chosen in a manner that attempts to maintain the additive genetic variability in phenotypes. Such a constraint maintains the nonindependence among observations under the null hypothesis of no linkage. The empirical distribution of the lod scores calculated using permuted phenotypes is compared to that obtained using phenotypes simulated from the assumed underlying multivariate normal model. We make comparisons of univariate analyses for both a quantitative phenotype that appears consistent with a multivariate normal model and a quantitative phenotype containing pronounced outliers. An example of a bivariate analysis is also presented.
ISSN:0741-0395
1098-2272
DOI:10.1002/gepi.1370170729