Brief Communication | Published:

Epigenome-wide association studies without the need for cell-type composition

Nature Methods volume 11, pages 309311 (2014) | Download Citation

Abstract

In epigenome-wide association studies, cell-type composition often differs between cases and controls, yielding associations that simply tag cell type rather than reveal fundamental biology. Current solutions require actual or estimated cell-type composition—information not easily obtainable for many samples of interest. We propose a method, FaST-LMM-EWASher, that automatically corrects for cell-type composition without the need for explicit knowledge of it, and then validate our method by comparison with the state-of-the-art approach. Corresponding software is available from http://www.microsoft.com/science/.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Accessions

Gene Expression Omnibus

References

  1. 1.

    et al. Nat. Biotechnol. 31, 142–147 (2013).

  2. 2.

    et al. Epigenetics 8, 816–826 (2013).

  3. 3.

    et al. PLoS ONE 7, e41361 (2012).

  4. 4.

    et al. Proc. Natl. Acad. Sci. USA 109 (suppl. 2), 17253–17260 (2012).

  5. 5.

    , , & Nat. Rev. Genet. 12, 529–541 (2011).

  6. 6.

    et al. Nat. Methods 8, 833–835 (2011).

  7. 7.

    et al. Nat. Methods 9, 525–526 (2012).

  8. 8.

    et al. Sci. Rep. 3, 1815 (2013).

  9. 9.

    et al. BMC Bioinformatics 13, 86 (2012).

  10. 10.

    , & Theor. Popul. Biol. 60, 155–166 (2001).

  11. 11.

    & Clin. Chem. Lab. Med. 50, 1707–1721 (2012).

  12. 12.

    , , , & Ann. Surg. Oncol. 13, 802–808 (2006).

  13. 13.

    The Cancer Genome Atlas Network. Nature 490, 61–70 (2012).

  14. 14.

    et al. Anesthesiology 116, 896–902 (2012).

  15. 15.

    et al. Oncogene 31, 527–534 (2012).

  16. 16.

    Nat. Rev. Genet. 7, 781–791 (2006).

  17. 17.

    & Biometrics 55, 997–1004 (1999).

  18. 18.

    et al. Eur. J. Hum. Genet. 19, 807–812 (2011).

  19. 19.

    , , & Nat. Rev. Genet. 11, 459–463 (2010).

  20. 20.

    , & Nucleic Acids Res. 37, 1–13 (2009).

  21. 21.

    , & Nat. Protoc. 4, 44–57 (2009).

Download references

Acknowledgements

We thank Y. Yamanaka for helpful feedback on the manuscript and D. Koestler, M. Kobor, G. Quon for useful discussions.

Author information

Affiliations

  1. eScience Research Group, Microsoft Research, Los Angeles, California, USA.

    • James Zou
    • , Christoph Lippert
    • , David Heckerman
    •  & Jennifer Listgarten
  2. The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

    • James Zou
  3. School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, USA.

    • James Zou
  4. Harvard Medical School, Boston, Massachusetts, USA.

    • Martin Aryee
  5. Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Martin Aryee

Authors

  1. Search for James Zou in:

  2. Search for Christoph Lippert in:

  3. Search for David Heckerman in:

  4. Search for Martin Aryee in:

  5. Search for Jennifer Listgarten in:

Contributions

J.Z. and J.L. designed research, performed research, contributed analytic tools, analyzed data and wrote the paper. C.L. and D.H. contributed analytic tools. M.A. designed research.

Competing interests

J.Z., C.L., D.H. and J.L. were employees of Microsoft at the time this work was performed.

Corresponding authors

Correspondence to James Zou or Jennifer Listgarten.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–12, Supplementary Tables 1–3 and Supplementary Notes 1 and 2.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/nmeth.2815

Further reading