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. 2004 Apr;74(4):765-9.
doi: 10.1086/383251. Epub 2004 Mar 2.

A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other

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A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other

Dale R Nyholt. Am J Hum Genet. 2004 Apr.

Abstract

In this report, we describe a simple correction for multiple testing of single-nucleotide polymorphisms (SNPs) in linkage disequilibrium (LD) with each other, on the basis of the spectral decomposition (SpD) of matrices of pairwise LD between SNPs. This method provides a useful alternative to more computationally intensive permutation tests. A user-friendly interface (SNPSpD) for performing this correction is available online (http://genepi.qimr.edu.au/general/daleN/SNPSpD/). Additionally, output from SNPSpD includes eigenvalues, principal-component coefficients, and factor "loadings" after varimax rotation, enabling the selection of a subset of SNPs that optimize the information in a genomic region.

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Figures

Figure  1
Figure 1
Probability (Pr) of a type I error plotted against the number of SNPs (in chromosomal order) tested in the Keavney et al. (1998) data. The graph shows the expected increase in the false-positive rate for completely independent SNPs [i.e., 1-(1-α)M] (thick dashed line), by use of an Meff-Šidák correction [i.e., 1-(1-α)Meff] (thin dashed line), and from 50,000 permutations (thick solid line), for α=0.05.

References

Electronic-Database Information

    1. SNP Spectral Decomposition (SNPSpD) Web Interface, http://genepi.qimr.edu.au/general/daleN/SNPSpD/
    1. LDMAX Program (Part of the GOLD Command Line Tools Package [gold-1.1.0.tar.gz]), http://www.sph.umich.edu/csg/abecasis/GOLD/download/index.html
    1. TCR α/δ Locus Data of Moffatt et al. (2000), http://www.well.ox.ac.uk/asthma/public/TCR/index.shtml

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