Commentary | Published:

The PsychENCODE project

Nature Neuroscience volume 18, pages 17071712 (2015) | Download Citation

Recent research on disparate psychiatric disorders has implicated rare variants in genes involved in global gene regulation and chromatin modification, as well as many common variants located primarily in regulatory regions of the genome. Understanding precisely how these variants contribute to disease will require a deeper appreciation for the mechanisms of gene regulation in the developing and adult human brain. The PsychENCODE project aims to produce a public resource of multidimensional genomic data using tissue- and cell type–specific samples from approximately 1,000 phenotypically well-characterized, high-quality healthy and disease-affected human post-mortem brains, as well as functionally characterize disease-associated regulatory elements and variants in model systems. We are beginning with a focus on autism spectrum disorder, bipolar disorder and schizophrenia, and expect that this knowledge will apply to a wide variety of psychiatric disorders. This paper outlines the motivation and design of PsychENCODE.

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References

  1. 1.

    et al. Nature 409, 860–921 (2001).

  2. 2.

    et al. Science 291, 1304–1351 (2001).

  3. 3.

    & Proc. Natl. Acad. Sci. USA 102, 4936–4942 (2005).

  4. 4.

    & Cell 152, 1237–1251 (2013).

  5. 5.

    , & Nature 461, 199–205 (2009).

  6. 6.

    Encode Project Consortium. Nature 489, 57–74 (2012).

  7. 7.

    Roadmap Epigenomics Consortium et al. Nature 518, 317–330 (2015).

  8. 8.

    & Nat. Biotechnol. 30, 1095–1106 (2012).

  9. 9.

    GTEx Consortium. Science 348, 648–660 (2015).

  10. 10.

    , & Nat. Rev. Genet. 13, 537–551 (2012).

  11. 11.

    Cross-Disorder Group of the Psychiatric Genomics Consortium et al. Nat. Genet. 45, 984–994 (2013).

  12. 12.

    et al. Neuron 62, 494–509 (2009).

  13. 13.

    , , & Neuron 85, 27–47 (2015).

  14. 14.

    , & Trends Genet. 31, 77–87 (2015).

  15. 15.

    et al. Neuron 75, 601–617 (2012).

  16. 16.

    & Proc. Natl. Acad. Sci. USA 105, 6987–6992 (2008).

  17. 17.

    et al. Nature 508, 199–206 (2014).

  18. 18.

    et al. Nature 478, 483–489 (2011).

  19. 19.

    et al. Nat. Neurosci. 18, 637–646 (2015).

  20. 20.

    et al. Proc. Natl. Acad. Sci. USA 112, 7285–7290 (2015).

  21. 21.

    & Nat. Rev. Neurosci. 7, 818–827 (2006).

  22. 22.

    Nature 468, 187–193 (2010).

  23. 23.

    et al. Lancet 373, 234–239 (2009).

  24. 24.

    & Front. Genet. 3, 118 (2012).

  25. 25.

    Psychiatric GWAS Consortium Bipolar Disorder Working Group. Nat. Genet. 43, 977–983 (2011).

  26. 26.

    Schizophrenia Working Group of the Psychiatric Genomics Consortium. Nature 511, 421–427 (2014).

  27. 27.

    & Cell 148, 1223–1241 (2012).

  28. 28.

    , & Trends Neurosci. 31, 137–145 (2008).

  29. 29.

    & Lancet Neurol 14, 1109–1120 (2015).

  30. 30.

    et al. Nature 515, 209–215 (2014).

  31. 31.

    et al. Nature 515, 216–221 (2014).

  32. 32.

    et al. Nat. Genet. 46, 881–885 (2014).

  33. 33.

    et al. Mol. Psychiatry 19, 652–658 (2014).

  34. 34.

    et al. Nature 506, 179–184 (2014).

  35. 35.

    , , , & BMC Neurosci. 9, 42 (2008).

  36. 36.

    et al. Cell 162, 375–390 (2015).

  37. 37.

    et al. Psychiatr. Genet. 21, 217–228 (2011).

  38. 38.

    , , & Curr. Protoc. Mol. Biol. 109, 21.29 (2015).

  39. 39.

    , & Nat. Rev. Genet. 14, 390–403 (2013).

  40. 40.

    et al. Genome Res. 25, 1206–1214 (2015).

  41. 41.

    et al. Genome Res. 22, 2497–2506 (2012).

  42. 42.

    et al. Nat. Methods 12, 458–464 (2015).

  43. 43.

    et al. Mol. Psychiatry 18, 340–346 (2013).

  44. 44.

    et al. Mol. Psychiatry 17, 193–201 (2012).

  45. 45.

    et al. Am. J. Hum. Genet. 95, 194–208 (2014).

  46. 46.

    et al. Nature 482, 390–394 (2012).

  47. 47.

    et al. Genome Biol. 12, R10 (2011).

  48. 48.

    et al. Am. J. Hum. Genet. 92, 667–680 (2013).

  49. 49.

    & Cold Spring Harb. Perspect. Biol. 3, a005744 (2011).

  50. 50.

    & Dis. Model. Mech. 5, 26–32 (2012).

Download references

Acknowledgements

The authors would like to acknowledge and thank the tissue donors and their families. We also thank all consortium members for discussions and feedback on this document. The PsychENCODE consortium projects are funded by the US National Institute of Mental Health.

Author information

Affiliations

  1. Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Schahram Akbarian
    • , Dalila Pinto
    • , Stella Dracheva
    • , Nancy Francoeur
    • , Menachem Fromer
    • , David H Kavanagh
    • , Yan Jiang
    • , Alexey Kozlenkov
    • , Marija Kundakovic
    • , Panos Roussos
    • , Robert Sebra
    • , Harm van Bakel
    •  & Pamela Sklar
  2. University of Illinois at Chicago, Chicago, Illinois, USA.

    • Chunyu Liu
    • , Kay Grennan
    • , Annie W Shieh
    •  & Yongjun Wang
  3. University of Southern California, Los Angeles, California, USA.

    • James A Knowles
    • , Peggy J Farnham
    • , Chris Armoskus
    • , Benjamin P Berman
    • , Gerhard A Coetzee
    • , Robert Gao
    • , Jennifer Herstein
    • , Shannon Schreiner
    • , Kai Wang
    • , Heather Witt
    •  & Lijing Yao
  4. Yale University, New Haven, Connecticut, USA.

    • Flora M Vaccarino
    • , Angus C Nairn
    • , Sirisha Pochareddy
    • , Sherman Weissman
    • , Mark B Gerstein
    • , Anahita Amiri
    • , Gianfilippo Coppola
    • , Robert R Kitchen
    • , Mingfeng Li
    • , Zhen Li
    • , Shuang Liu
    • , Fábio C P Navarro
    • , Soraya Scuderi
    • , Mikihito Shibata
    • , Mario Skarica
    • , Daifeng Wang
    • , Xuming Xu
    •  & Nenad Sestan
  5. Duke University, Durham, North Carolina, USA.

    • Gregory E Crawford
    • , Allison E Ashley-Koch
    • , Timothy E Reddy
    •  & Gregory A Wray
  6. Lieber Institute for Brain Development, Baltimore, Maryland, USA.

    • Andrew E Jaffe
    • , Nikolay A Ivanov
    •  & Amanda J Price
  7. University of California, Los Angeles, California, USA.

    • Daniel H Geschwind
    • , Neelroop Parikshak
    • , Vivek Swarup
    • , Hyejung Won
    •  & Emily Y Wu
  8. King's College London, London, and University of Exeter, Devon, UK.

    • Jonathan Mill
    • , Jeremie Poschmann
    •  & Chloe C Y Wong
  9. Mayo Clinic, Rochester, Minnesota, USA.

    • Alexej Abyzov
    •  & Taejeong Bae
  10. Genome Institute of Singapore, Singapore.

    • Shyam Prabhakar
    •  & Wenjie Sun
  11. University of North Carolina, Chapel Hill, North Carolina, USA.

    • Patrick F Sullivan
  12. University of California, San Francisco, California, USA.

    • Matthew W State
    • , Eirene Markenscoff-Papadimitriou
    • , Donna M Werling
    •  & A Jeremy Willsey
  13. University of Massachusetts Medical School, Worcester, Massachusetts, USA.

    • Zhiping Weng
    • , Eugenio Mattei
    • , Michael Purcaro
    •  & Junko Tsuji
  14. Sage Bionetworks, Seattle, Washington, USA.

    • Mette A Peters
    • , Lara M Mangravite
    •  & Larsson Omberg
  15. The University of Chicago, Chicago, Illinois, USA.

    • Kevin P White
    •  & Amber Thomas
  16. National Institute of Mental Health, Bethesda, Maryland, USA.

    • Andrea Beckel-Mitchener
    • , Nicole North
    • , David Panchision
    • , Geetha Senthil
    •  & Thomas Lehner

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Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Geetha Senthil or Thomas Lehner or Pamela Sklar or Nenad Sestan.

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DOI

https://doi.org/10.1038/nn.4156

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