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Theoretical Formulation of Principal Components Analysis to Detect and Correct for Population Stratification

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  • Jianzhong Ma
  • Christopher I Amos

Abstract

The Eigenstrat method, based on principal components analysis (PCA), is commonly used both to quantify population relationships in population genetics and to correct for population stratification in genome-wide association studies. However, it can be difficult to make appropriate inference about population relationships from the principal component (PC) scatter plot. Here, to better understand the working mechanism of the Eigenstrat method, we consider its theoretical or “population” formulation. The eigen-equation for samples from an arbitrary number () of populations is reduced to that of a matrix of dimension , the elements of which are determined by the variance-covariance matrix for the random vector of the allele frequencies. Solving the reduced eigen-equation is numerically trivial and yields eigenvectors that are the axes of variation required for differentiating the populations. Using the reduced eigen-equation, we investigate the within-population fluctuations around the axes of variation on the PC scatter plot for simulated datasets. Specifically, we show that there exists an asymptotically stable pattern of the PC plot for large sample size. Our results provide theoretical guidance for interpreting the pattern of PC plot in terms of population relationships. For applications in genetic association tests, we demonstrate that, as a method of correcting for population stratification, regressing out the theoretical PCs corresponding to the axes of variation is equivalent to simply removing the population mean of allele counts and works as well as or better than the Eigenstrat method.

Suggested Citation

  • Jianzhong Ma & Christopher I Amos, 2010. "Theoretical Formulation of Principal Components Analysis to Detect and Correct for Population Stratification," PLOS ONE, Public Library of Science, vol. 5(9), pages 1-14, September.
  • Handle: RePEc:plo:pone00:0012510
    DOI: 10.1371/journal.pone.0012510
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    References listed on IDEAS

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    1. B. Devlin & Kathryn Roeder, 1999. "Genomic Control for Association Studies," Biometrics, The International Biometric Society, vol. 55(4), pages 997-1004, December.
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    1. Jianzhong Ma & Christopher I Amos, 2012. "Investigation of Inversion Polymorphisms in the Human Genome Using Principal Components Analysis," PLOS ONE, Public Library of Science, vol. 7(7), pages 1-12, July.
    2. Jianzhong Ma & Christopher I Amos, 2012. "Principal Components Analysis of Population Admixture," PLOS ONE, Public Library of Science, vol. 7(7), pages 1-12, July.
    3. Zheng, Xiuwen & Weir, Bruce S., 2016. "Eigenanalysis of SNP data with an identity by descent interpretation," Theoretical Population Biology, Elsevier, vol. 107(C), pages 65-76.

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