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Enhancing GTEx by bridging the gaps between genotype, gene expression, and disease

Nature Genetics volume 49, pages 1664–1670 (2017)Cite this article

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Genetic variants have been associated with myriad molecular phenotypes that provide new insight into the range of mechanisms underlying genetic traits and diseases. Identifying any particular genetic variant's cascade of effects, from molecule to individual, requires assaying multiple layers of molecular complexity. We introduce the Enhancing GTEx (eGTEx) project that extends the GTEx project to combine gene expression with additional intermediate molecular measurements on the same tissues to provide a resource for studying how genetic differences cascade through molecular phenotypes to impact human health.

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Figure 1: Quantifying layers of molecular and cellular phenotypes.

References

  1. Nicolae, D.L. et al. PLoS Genet. 6, e1000888 (2010).

    Article  Google Scholar 

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

  3. Degner, J.F. et al. Nature 482, 390–394 (2012).

    Article  CAS  Google Scholar 

  4. McVicker, G. et al. Science 342, 747–749 (2013).

    Article  CAS  Google Scholar 

  5. Sun, W. Biometrics 68, 1–11 (2012).

    Article  Google Scholar 

  6. van de Geijn, B., McVicker, G., Gilad, Y. & Pritchard, J.K. Nat. Methods 12, 1061–1063 (2015).

    Article  CAS  Google Scholar 

  7. Kumasaka, N., Knights, A.J. & Gaffney, D.J. Nat. Genet. 48, 206–213 (2016).

    Article  CAS  Google Scholar 

  8. Lappalainen, T. et al. Nature 501, 506–511 (2013).

    Article  CAS  Google Scholar 

  9. Li, Y.I. et al. Science 352, 600–604 (2016).

    Article  CAS  Google Scholar 

  10. Gibbs, J.R. et al. PLoS Genet. 6, e1000952 (2010).

    Article  Google Scholar 

  11. Bell, J.T. et al. Genome Biol. 12, R10 (2011).

    Article  CAS  Google Scholar 

  12. Gutierrez-Arcelus, M. et al. eLife 2, e00523 (2013).

    Article  Google Scholar 

  13. Wu, L. et al. Nature 499, 79–82 (2013).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  15. Banovich, N.E. et al. PLoS Genet. 10, e1004663 (2014).

    Article  Google Scholar 

  16. Gutierrez-Arcelus, M. et al. PLoS Genet. 11, e1004958 (2015).

    Article  Google Scholar 

  17. Battle, A. et al. Science 347, 664–667 (2015).

    Article  CAS  Google Scholar 

  18. Cenik, C. et al. Genome Res. 25, 1610–1621 (2015).

    Article  CAS  Google Scholar 

  19. Ritchie, M.D., Holzinger, E.R., Li, R., Pendergrass, S.A. & Kim, D. Nat. Rev. Genet. 16, 85–97 (2015).

    Article  CAS  Google Scholar 

  20. Vucic, E.A. et al. Genome Res. 22, 188–195 (2012).

    Article  CAS  Google Scholar 

  21. Rooney, M.S., Shukla, S.A., Wu, C.J., Getz, G. & Hacohen, N. Cell 160, 48–61 (2015).

    Article  CAS  Google Scholar 

  22. Fernandez-Banet, J. et al. Nat. Methods 13, 9–10 (2016).

    Article  CAS  Google Scholar 

  23. Kosti, I., Jain, N., Aran, D., Butte, A.J. & Sirota, M. Sci. Rep. 6, 24799 (2016).

    Article  CAS  Google Scholar 

  24. Carithers, L.J. et al. Biopreserv. Biobank. 13, 311–319 (2015).

    Article  Google Scholar 

  25. GTEx Consortium. Nature http://dx.doi.org/10.1038/nature24277 (2017).

  26. Li, X. et al. Nature http://dx.doi.org/10.1038/nature24267 (2017).

  27. Weintraub, H. & Groudine, M. Science 193, 848–856 (1976).

    Article  CAS  Google Scholar 

  28. Wu, C., Wong, Y.C. & Elgin, S.C. Cell 16, 807–814 (1979).

    Article  CAS  Google Scholar 

  29. Maurano, M.T. et al. Science 337, 1190–1195 (2012).

    Article  CAS  Google Scholar 

  30. Maurano, M.T. et al. Nat. Genet. 47, 1393–1401 (2015).

    Article  CAS  Google Scholar 

  31. Neph, S. et al. Nature 489, 83–90 (2012).

    Article  CAS  Google Scholar 

  32. Bannister, A.J. & Kouzarides, T. Cell Res. 21, 381–395 (2011).

    Article  CAS  Google Scholar 

  33. Ernst, J. et al. Nature 473, 43–49 (2011).

    Article  CAS  Google Scholar 

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

  35. Kasowski, M. et al. Science 342, 750–752 (2013).

    Article  CAS  Google Scholar 

  36. Maurano, M.T. et al. Cell Rep. 12, 1184–1195 (2015).

    Article  CAS  Google Scholar 

  37. Pervjakova, N. et al. Epigenomics 8, 789–799 (2016).

    Article  CAS  Google Scholar 

  38. Li, E., Beard, C. & Jaenisch, R. Nature 366, 362–365 (1993).

    Article  CAS  Google Scholar 

  39. Payer, B. & Lee, J.T. Annu. Rev. Genet. 42, 733–772 (2008).

    Article  CAS  Google Scholar 

  40. Curradi, M., Izzo, A., Badaracco, G. & Landsberger, N. Mol. Cell. Biol. 22, 3157–3173 (2002).

    Article  CAS  Google Scholar 

  41. Castel, S.E., Levy-Moonshine, A., Mohammadi, P., Banks, E. & Lappalainen, T. Genome Biol. 16, 195 (2015).

    Article  Google Scholar 

  42. Zhang, R. et al. Nat. Methods 11, 51–54 (2014).

    Article  CAS  Google Scholar 

  43. Kukurba, K.R. et al. PLoS Genet. 10, e1004304 (2014).

    Article  Google Scholar 

  44. Rivas, M.A. et al. Science 348, 666–669 (2015).

    Article  CAS  Google Scholar 

  45. Baran, Y. et al. Genome Res. 25, 927–936 (2015).

    Article  CAS  Google Scholar 

  46. Pirinen, M. et al. Bioinformatics 31, 2497–2504 (2015).

    Article  CAS  Google Scholar 

  47. Dominissini, D. et al. Nature 485, 201–206 (2012).

    Article  CAS  Google Scholar 

  48. Meyer, K.D. et al. Cell 149, 1635–1646 (2012).

    Article  CAS  Google Scholar 

  49. Ciaccio, M.F., Wagner, J.P., Chuu, C.P., Lauffenburger, D.A. & Jones, R.B. Nat. Methods 7, 148–155 (2010).

    Article  CAS  Google Scholar 

  50. O'Huallachain, M., Karczewski, K.J., Weissman, S.M., Urban, A.E. & Snyder, M.P. Proc. Natl. Acad. Sci. USA 109, 18018–18023 (2012).

    Article  CAS  Google Scholar 

  51. Haycock, P.C. et al. Br. Med. J. 349, g4227 (2014).

    Article  Google Scholar 

  52. Stone, R.C. et al. PLoS Genet. 12, e1006144 (2016).

    Article  Google Scholar 

  53. Kibriya, M.G., Jasmine, F., Roy, S., Ahsan, H. & Pierce, B. Cancer Epidemiol. Biomarkers Prev. 23, 2667–2672 (2014).

    Article  CAS  Google Scholar 

  54. Pierce, B.L. et al. Int. J. Mol. Epidemiol. Genet. 7, 18–23 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Kibriya, M.G., Jasmine, F., Roy, S., Ahsan, H. & Pierce, B.L. PLoS One 11, e0155548 (2016).

    Article  Google Scholar 

  56. Jagannathan, S. & Bradley, R.K. Genome Res. 26, 1639–1650 (2016).

    Article  CAS  Google Scholar 

  57. Gamazon, E.R. et al. Nat. Genet. 47, 1091–1098 (2015).

    Article  CAS  Google Scholar 

  58. Nica, A.C. et al. PLoS Genet. 6, e1000895 (2010).

    Article  Google Scholar 

  59. Hormozdiari, F. et al. Am. J. Hum. Genet. 99, 1245–1260 003 (2016).

    Article  CAS  Google Scholar 

  60. Civelek, M. & Lusis, A.J. Nat. Rev. Genet. 15, 34–48 (2014).

    Article  CAS  Google Scholar 

  61. Parikshak, N.N., Gandal, M.J. & Geschwind, D.H. Nat. Rev. Genet. 16, 441–458 (2015).

    Article  CAS  Google Scholar 

  62. Zhu, J. et al. PLoS Biol. 10, e1001301 (2012).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The Genotype-Tissue Expression (GTEx) project was supported by the Common Fund of the Office of the Director of the US National Institutes of Health (NIH; see URLs). Additional funds were provided by the National Cancer Institute (NCI), National Human Genome Research Institute (NHGRI), National Heart, Lung, and Blood Institute (NHLBI), National Institute on Drug Abuse (NIDA), National Institute of Mental Health (NIMH), and National Institute of Neurological Disorders and Stroke (NINDS). Donors were enrolled at Biospecimen Source Sites funded by Leidos Biomedical. Leidos subcontracts to the National Disease Research Interchange (10XS170) and the Roswell Park Cancer Institute (10XS171). The LDACC was funded through a contract (HHSN268201000029C) to the Broad Institute. Biorepository operations were funded through a Leidos subcontract to the Van Andel Research Institute (10ST1035). Additional data repository and project management were provided by Leidos (HHSN261200800001E). The Brain Bank was supported by a supplement to University of Miami grant DA006227. E.K.T. is supported by a Hewlett-Packard Stanford Graduate Fellowship and a doctoral scholarship from the Natural Science and Engineering Council of Canada. NIH grant U01MH104393 supported A.P.F., K.D.H., L.F.R., and P.F.H. NIH grant U01HG007598 supported B.E.S. NIH grant U01HG007599 supported J.A.S. NIH grant U01HG007593 supported J.B.L. and S.B.M. NIH grant U01HG007591 supported J.M.A. NIH grant U01HG007610 supported M.K. NIH grant U01HG007601 supported B.L.P. NIH grant U01HL131042 supported M.P.S. and H.T.

Author information

Authors and Affiliations

  1. Department of Medicine, Section of Genetic Medicine, University of Chicago, Chicago, Illinois, USA

    Barbara E Stranger, Marian S Fernando, Caroline Linke, Meritxell Oliva, Andrew Skol & Fan Wu

  2. Institute for Genomics and Systems Biology, University of Chicago, Chicago, Illinois, USA

    Barbara E Stranger, Marian S Fernando, Caroline Linke, Meritxell Oliva, Andrew Skol & Fan Wu

  3. Center for Data-Intensive Science, University of Chicago, Chicago, Illinois, USA

    Barbara E Stranger & Andrew Skol

  4. Washington Regional Transplant Community, Annandale, Virginia, USA

    Lori E Brigham

  5. Gift of Life Donor Program, Philadelphia, Pennsylvania, USA

    Richard Hasz

  6. LifeGift, Houston, Texas, USA

    Marcus Hunter, Kevin Myer & Brian Roe

  7. Center for Organ Recovery and Education, Pittsburgh, Pennsylvania, USA

    Christopher Johns & Joseph Wheeler

  8. LifeNet Health, Virginia Beach, Virginia, USA

    Mark Johnson, Gary Walters & Michael Washington

  9. National Disease Research Interchange, Philadelphia, Pennsylvania, USA

    Gene Kopen, William F Leinweber, John T Lonsdale, Alisa McDonald, Bernadette Mestichelli, Michael Salvatore, Saboor Shad & Jeffrey A Thomas

  10. Unyts, Buffalo, New York, USA

    Jason Bridge

  11. Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York, USA

    Barbara A Foster, Bryan M Gillard, Ellen Karasik, Rachna Kumar, Mark Miklos & Michael T Moser

  12. Van Andel Research Institute, Grand Rapids, Michigan, USA

    Scott D Jewell, Robert G Montroy, Daniel C Rohrer & Dana R Valley

  13. Brain Endowment Bank, Miller School of Medicine, University of Miami, Miami, Florida, USA

    David A Davis & Deborah C Mash

  14. Division of Genomic Medicine, National Human Genome Research Institute, Rockville, Maryland, USA

    Sarah E Gould, Casey Martin, Jeffery P Struewing & Simona Volpi

  15. Division of Cancer Treatment and Diagnosis, Biorepositories and Biospecimen Research Branch, National Cancer Institute, Bethesda, Maryland, USA

    Ping Guan, Helen M Moore & Abhi Rao

  16. Division of Neuroscience and Basic Behavioral Science, National Institute of Mental Health, US National Institutes of Health, Bethesda, Maryland, USA

    Susan Koester

  17. National Institute on Drug Abuse, US National Institutes of Health, Bethesda, Maryland, USA

    A Roger Little

  18. Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Kasper D Hansen, Lindsay F Rizzardi & Andrew P Feinberg

  19. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA

    Kasper D Hansen

  20. Department of Biostatistics, Johns Hopkins University, Baltimore, Maryland, USA

    Kasper D Hansen & Peter F Hickey

  21. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    Lei Hou, Yaping Liu, Yongjin Park, Nicola Rinaldi & Manolis Kellis

  22. Broad Institute of MIT and Harvard University, Cambridge, Massachusetts, USA

    Lei Hou, Yaping Liu, Benoit Molinie, Yongjin Park, Nicola Rinaldi, Li Wang, Nicholas Van Wittenberghe, Melina Claussnitzer, Ellen T Gelfand, Kristin G Ardlie & Manolis Kellis

  23. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

    Melina Claussnitzer

  24. Department of Natural Science, University of Hohenheim, Stuttgart, Germany

    Melina Claussnitzer

  25. Department of Genetics, Stanford University, Stanford, California, USA

    Qin Li, Sandra Linder, Rui Zhang, Lihua Jiang, Shin Lin, Meng Wang, Ruiqi Jian, Xiao Li, Joanne Chan, Jin Billy Li, Hua Tang, Michael P Snyder & Stephen B Montgomery

  26. Department of Pathology, Stanford University, Stanford, California, USA

    Sandra Linder, Kevin S Smith, Emily K Tsang & Stephen B Montgomery

  27. Biomedical Informatics Program, Stanford University, Stanford, California, USA

    Emily K Tsang

  28. Department of Public Health Sciences, University of Chicago, Chicago, Illinois, USA

    Lin S Chen, Kathryn Demanelis, Farzana Jasmine, Muhammad G Kibriya & Brandon L Pierce

  29. Department of Population Health Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA

    Jennifer A Doherty

  30. Division of Cardiology, University of Washington, Seattle, Washington, USA

    Shin Lin

  31. Altius Institute for Biomedical Sciences, Seattle, Washington, USA

    Daniel Bates, Morgan Diegel, Jessica Halow, Eric Haugen, Audra Johnson, Rajinder Kaul, Kristen Lee, Jemma Nelson, Fidencio J Neri, Richard Sandstrom & John A Stamatoyannopoulos

  32. Institute for Systems Genetics, New York University Langone Medical Center, New York, New York, USA

    Matthew T Maurano

  33. Lewis Sigler Institute, Princeton University, Princeton, New Jersey, USA

    Joshua M Akey

  34. Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey, USA

    Joshua M Akey

  35. Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA

    Andrew P Feinberg

  36. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Andrew P Feinberg

  37. Department of Mental Health, Johns Hopkins University School of Public Health, Baltimore, Maryland, USA

    Andrew P Feinberg

  38. Department of Medicine, University of Washington, Seattle, Washington, USA

    John A Stamatoyannopoulos

  39. Department of Genome Sciences, University of Washington, Seattle, Washington, USA

    John A Stamatoyannopoulos

Consortia

eGTEx Project

  • Barbara E Stranger
  • , Lori E Brigham
  • , Richard Hasz
  • , Marcus Hunter
  • , Christopher Johns
  • , Mark Johnson
  • , Gene Kopen
  • , William F Leinweber
  • , John T Lonsdale
  • , Alisa McDonald
  • , Bernadette Mestichelli
  • , Kevin Myer
  • , Brian Roe
  • , Michael Salvatore
  • , Saboor Shad
  • , Jeffrey A Thomas
  • , Gary Walters
  • , Michael Washington
  • , Joseph Wheeler
  • , Jason Bridge
  • , Barbara A Foster
  • , Bryan M Gillard
  • , Ellen Karasik
  • , Rachna Kumar
  • , Mark Miklos
  • , Michael T Moser
  • , Scott D Jewell
  • , Robert G Montroy
  • , Daniel C Rohrer
  • , Dana R Valley
  • , David A Davis
  • , Deborah C Mash
  • , Sarah E Gould
  • , Ping Guan
  • , Susan Koester
  • , A Roger Little
  • , Casey Martin
  • , Helen M Moore
  • , Abhi Rao
  • , Jeffery P Struewing
  • , Simona Volpi
  • , Kasper D Hansen
  • , Peter F Hickey
  • , Lindsay F Rizzardi
  • , Lei Hou
  • , Yaping Liu
  • , Benoit Molinie
  • , Yongjin Park
  • , Nicola Rinaldi
  • , Li Wang
  • , Nicholas Van Wittenberghe
  • , Melina Claussnitzer
  • , Ellen T Gelfand
  • , Qin Li
  • , Sandra Linder
  • , Rui Zhang
  • , Kevin S Smith
  • , Emily K Tsang
  • , Lin S Chen
  • , Kathryn Demanelis
  • , Jennifer A Doherty
  • , Farzana Jasmine
  • , Muhammad G Kibriya
  • , Lihua Jiang
  • , Shin Lin
  • , Meng Wang
  • , Ruiqi Jian
  • , Xiao Li
  • , Joanne Chan
  • , Daniel Bates
  • , Morgan Diegel
  • , Jessica Halow
  • , Eric Haugen
  • , Audra Johnson
  • , Rajinder Kaul
  • , Kristen Lee
  • , Matthew T Maurano
  • , Jemma Nelson
  • , Fidencio J Neri
  • , Richard Sandstrom
  • , Marian S Fernando
  • , Caroline Linke
  • , Meritxell Oliva
  • , Andrew Skol
  • , Fan Wu
  • , Joshua M Akey
  • , Andrew P Feinberg
  • , Jin Billy Li
  • , Brandon L Pierce
  • , John A Stamatoyannopoulos
  • , Hua Tang
  • , Kristin G Ardlie
  • , Manolis Kellis
  • , Michael P Snyder
  •  & Stephen B Montgomery

Contributions

All authors contributed to study design. L.E.B., R.H., M.H., C.J., M.J., G.K., W.F.L., J.T.L., A.M., B. Mestichelli, K.M., B.R., M.S., S.S., J.A.T., G.W., M. Washington, J.W., J.B., B.A.F., B.M.G., E.K., R. Kumar, M.M., M.T. Moser, S.D.J., R.G.M., D.C.R., D.R.V., D.A.D., and D.C.M. were part of the biospecimen collection group. S.E.G., P.G., S.K., A.R.L., C.M., H.M.M., A.R., J.P.S., and S.V. were NIH program management. K.D.H., P.F.H., L.F.R., L.H., Y.L., B. Molinie, Y.P., N.R., L.W., N.V.W., M.C., E.T.G., Q.L., S. Linder, R.Z., K.S.S., E.K.T., L.S.C., K.D., J.A.D., F.J., M.G.K., L.J., S. Lin, M. Wang, R.J., X.L., J.C., D.B., M.D., J.H., E.H., A.J., R. Kaul, K.L., M.T. Maurano, J.N., F.J.N., R.S., M.S.F., C.L., M.O., A.S., F.W., J.M.A., A.P.F., J.B.L., B.L.P., J.A.S., H.T., K.G.A., M.K., M.P.S., S.B.M., and B.E.S. were part of the eGTEx project working group. The writing group included E.K.T., J.M.A., M.T. Maurano, H.T., M.S., S.V., R. Kaul, J.A.S., L.F.R., B.L.P., H.M.M., K.G.A., M.K., S.B.M., and B.E.S. and was led by K.G.A., M.K., M.P.S., S.B.M., and B.E.S.

Corresponding authors

Correspondence to Barbara E Stranger, Kristin G Ardlie, Manolis Kellis, Michael P Snyder or Stephen B Montgomery.

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Competing interests

M.P.S. is a cofounder of Personalis and Q bio and is on the scientific advisory boards of Personalis, Epinomics, and Genapsys.

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eGTEx Project. Enhancing GTEx by bridging the gaps between genotype, gene expression, and disease. Nat Genet 49, 1664–1670 (2017). https://doi.org/10.1038/ng.3969

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