Robust LOD scores for variance component-based linkage analysis

John Blangero, Jeff T. Williams, Lauras Almasy

    Research output: Contribution to journalArticle

    142 Scopus citations

    Abstract

    The variance component method is now widely used for linkage analysis of quantitative traits. Although this approach offers many advantages, the importance of the underlying assumption of multivariate normality of the trait distribution within pedigrees has not been studied extensively. Simulation studies have shown that traits with leptokurtic distributions yield linkage test statistics that exhibit excessive Type I error when analyzed naively. We derive analytical formulae relating the deviation from the expected asymptotic distribution of the lod score to the kurtosis and total heritability of the quantitative trait. A simple correction constant yields a robust lod score for any deviation from normality and for any pedigree structure, and effectively eliminates the problem of inflated Type I error due to misspecification of the underlying probability model in variance component-based linkage analysis. (C) 2000 Wiley-Liss, Inc.

    Original languageEnglish (US)
    Pages (from-to)S8-S14
    JournalGenetic epidemiology
    Volume19
    Issue numberSUPPL. 1
    DOIs
    StatePublished - 2000

    Keywords

    • Kurtosis
    • Misspecification theory
    • Nonnormality
    • Statistical genetics

    ASJC Scopus subject areas

    • Epidemiology
    • Genetics(clinical)

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