Improving the Power of Sib Pair Quantitative Trait Loci Detection by Phenotype WinsorizationFernàndez J.R.a-c · Etzel C.d · Beasley T.M.b · Shete S.d · Amos C.I.d · Allison D.B.b,c
aDepartment of Nutrition Sciences, Division of Physiology and Metabolism, bDepartment of Biostatistics, cClinical Nutrition Research Center, The University of Alabama at Birmingham, Birmingham, Ala., dUniversity of Texas, M.D. Anderson Cancer Center, Houston, Tex., USA
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Objectives: In sib pair studies, quantitative trait loci (QTL) identification may be adversely affected by non-normality in the phenotypic distribution, particularly when subjects falling in the tails of the distribution bias the trait mean or variance. We evaluated the robustness and power of reducing the influence of subjects with extreme phenotypic values by Winsorizing non-normal distributions in three versions of Haseman-Elston regression-based methods of QTL linkage analysis. Methods: Data were simulated for normal and non-normal distributions. Phenotypic values that correspond to cutoff points at the ω and 1 – ω percentiles of the distribution were identified, and phenotypic values falling outside the boundaries of the ω and 1 – ω cutoff points were replaced by the ω and 1 – ω values, respectively. One million replications were performed for the three tests of linkage for Winsorized and non-Winsorized data. Results: Winsorization reduced conservatism in the tails of the empirical type I error rate for the vast majority of the tests of linkage, increased the power of QTL detection in non-normal data and created a slight negative bias in symmetrical phenotypic distributions. Conclusions: Winsorizing can improve the power of QTL detection with certain non-normal distributions but can also introduce bias into the estimate of the QTL effect.
© 2002 S. Karger AG, Basel
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