An Evaluation of Power and Type I Error of Single-Nucleotide Polymorphism Transmission/Disequilibrium-Based Statistical Methods under Different Family Structures, Missing Parental Data, and Population Stratification

KK Nicodemus, A Luna, Y Yao Shugart

    Research output: Contribution to journalArticle (Academic Journal)

    13 Citations (Scopus)

    Abstract

    Researchers conducting family-based association studies have a wide variety of transmission/disequilibrium (TD)-based methods to choose from, but few guidelines exist in the selection of a particular method to apply to available data. Using a simulation study design, we compared the power and type I error of eight popular TD-based methods under different family structures, frequencies of missing parental data, genetic models, and population stratifications. No method was uniformly most powerful under all conditions, but type I error was appropriate for nearly every test statistic under all conditions. Power varied widely across methods, with a 46.5% difference in power observed between the most powerful and the least powerful method when 50% of families consisted of an affected sib pair and one parent genotyped under an additive genetic model and a 35.2% difference when 50% of families consisted of a single affection-discordant sibling pair without parental genotypes available under an additive genetic model. Methods were generally robust to population stratification, although some slightly less so than others. The choice of a TD-based test statistic should be dependent on the predominant family structure ascertained, the frequency of missing parental genotypes, and the assumed genetic model.
    Translated title of the contributionAn Evaluation of Power and Type I Error of Single-Nucleotide Polymorphism Transmission/Disequilibrium-Based Statistical Methods under Different Family Structures, Missing Parental Data, and Population Stratification
    Original languageEnglish
    Pages (from-to)178 - 185
    Number of pages8
    JournalAmerican Journal of Human Genetics
    Volume80 (1)
    DOIs
    Publication statusPublished - Jan 2007

    Bibliographical note

    Publisher: University of Chicago Press

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