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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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Figure 1: Quantifying layers of molecular and cellular phenotypes.

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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.

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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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