Theoretical formulation of principal components analysis to detect and correct for population stratification.
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 pop...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-09-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2941459?pdf=render |
| _version_ | 1811322566787203072 |
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| author | Jianzhong Ma Christopher I Amos |
| author_facet | Jianzhong Ma Christopher I Amos |
| author_sort | Jianzhong Ma |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T13:38:32Z |
| format | Article |
| id | doaj.art-df6b567121d24167b5805f946c8eff86 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T13:38:32Z |
| publishDate | 2010-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-df6b567121d24167b5805f946c8eff862022-12-22T02:44:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-09-015910.1371/journal.pone.0012510Theoretical formulation of principal components analysis to detect and correct for population stratification.Jianzhong MaChristopher I AmosThe 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.http://europepmc.org/articles/PMC2941459?pdf=render |
| spellingShingle | Jianzhong Ma Christopher I Amos Theoretical formulation of principal components analysis to detect and correct for population stratification. PLoS ONE |
| title | Theoretical formulation of principal components analysis to detect and correct for population stratification. |
| title_full | Theoretical formulation of principal components analysis to detect and correct for population stratification. |
| title_fullStr | Theoretical formulation of principal components analysis to detect and correct for population stratification. |
| title_full_unstemmed | Theoretical formulation of principal components analysis to detect and correct for population stratification. |
| title_short | Theoretical formulation of principal components analysis to detect and correct for population stratification. |
| title_sort | theoretical formulation of principal components analysis to detect and correct for population stratification |
| url | http://europepmc.org/articles/PMC2941459?pdf=render |
| work_keys_str_mv | AT jianzhongma theoreticalformulationofprincipalcomponentsanalysistodetectandcorrectforpopulationstratification AT christopheriamos theoreticalformulationofprincipalcomponentsanalysistodetectandcorrectforpopulationstratification |