HUMAN GENETICS

Sizing up whole-genome sequencing studies of common diseases

The triplet code underpins analyses of rare and de novo mutations in exome sequencing data, but analysis of the noncoding genome is much more challenging. A new analytical framework for common, complex diseases highlights the need for very large samples to overcome the unavoidable multiple-testing burden and hence provides preemptive warnings against underpowered studies.

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Fig. 1: CWAS in the context of other experimental designs for investigating genetic variation in ASD.

References

  1. 1.

    Turner, T. N. et al. Cell 171, 710–722 (2017).

  2. 2.

    Short, P. J. et al. Nature 555, 611–616 (2018).

  3. 3.

    Werling, D. M. et al. Nat. Genet. https://doi.org/10.1038/s41588-018-0107-y (2018).

  4. 4.

    Finucane, H. K. et al. Nat. Genet. 47, 1228–1235 (2015).

  5. 5.

    Taylor, J. C. et al. Nat. Genet. 47, 717–726 (2015).

  6. 6.

    Costain, G. et al. Eur. J. Hum. Genet. https://doi.org/10.1038/s41431-018-0114-6 (2018).

  7. 7.

    Meynert, A. M., Ansari, M., FitzPatrick, D. R. & Taylor, M. S. BMC Bioinformatics 15, 247 (2014).

  8. 8.

    SPARK Consortium. Neuron 97, 488–493 (2018).

  9. 9.

    Deciphering Developmental Disorders Study. Nature 542, 433–438 (2017).

  10. 10.

    Fuchsberger, C. et al. Nature 536, 41–47 (2016).

  11. 11.

    Genovese, G. et al. Nat. Neurosci. 19, 1433–1441 (2016).

  12. 12.

    Luo, Y. et al. Nat. Genet. 49, 186–192 (2017).

  13. 13.

    Sanders, S. J. et al. Nat. Neurosci. 20, 1661–1668 (2017).

  14. 14.

    Mahajan, A. et al. Preprint at bioRxiv https://doi.org/10.1101/245506 (2018).

  15. 15.

    Collins, R. L. et al. Genome Biol. 18, 36 (2017).

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Correspondence to Naomi R. Wray or Jacob Gratten.

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Wray, N.R., Gratten, J. Sizing up whole-genome sequencing studies of common diseases. Nat Genet 50, 635–637 (2018). https://doi.org/10.1038/s41588-018-0113-0

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