Commentary

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

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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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

Affiliations

  1. Section of Genetic Medicine, Department of 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. Biorepositories and Biospecimen Research Branch, Division of Cancer Treatment and Diagnosis, 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. Huntsman Cancer Institute, Department of Population Health Sciences, 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

  1. eGTEx Project

Authors

    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.

    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.

    Corresponding authors

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