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Response to Sul and Eskin

Nature Reviews Genetics volume 14, page 300 (2013)Cite this article

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We thank Sul and Eskin (Mixed models can correct for population structure for genomic regions under selection. Nature Reviews Genetics 26 Feb 2013 (doi:10.1038/nrg2813-c1))1 for carefully examining and confirming the limitation of standard mixed model association methods that we identified in our Progress article (New approaches to population stratification in genome-wide association studies. Nature Reviews Genetics 11, 459–463 (2010))2 and for developing an interesting new way to address it.

In our article2, we investigated the limits of mixed model methods by considering an extreme simulation in which most markers had low population differentiation (FST = 0.01), but a small fraction of markers were unusually differentiated (allele frequency difference = 0.6). We found that standard mixed model methods3 did not fully correct for population structure, but mixed models with principal component covariates4 did fully correct for population structure. We stated that “population structure is a fixed effect, and spurious associations might result if it is modelled as a random effect based on overall covariance”.

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References

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Acknowledgements

We are grateful to E. Eskin, P. Visscher, J. Yang and M. Goddard for helpful discussions.

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Authors and Affiliations

  1. Alkes L. Price is at the Department of Epidemiology, USA; the Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, Harvard School of Public Health, Boston, Massachusetts 02115, USA; and the Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.,

    Alkes L. Price

  2. the Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA,

    Alkes L. Price

  3. Noah A. Zaitlen is at the Department of Medicine, Lung Biology Center, University of California San Francisco, San Francisco, California 94158, USA.,

    Noah A. Zaitlen

  4. USA; and the Department of Genetics, David Reich is at the Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, Harvard Medical School, Boston, Massachusetts 02115, USA.,

    David Reich

  5. and the Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.,

    David Reich

  6. Nick Patterson is at the Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.,

    Nick Patterson

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  1. Alkes L. Price
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Correspondence to Alkes L. Price.

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Price, A., Zaitlen, N., Reich, D. et al. Response to Sul and Eskin. Nat Rev Genet 14, 300 (2013). https://doi.org/10.1038/nrg2813-c2

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