@article{cd766b254c7747d0a1703783aabd9318,
title = "Genetic effects on gene expression across human tissues",
abstract = "Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.",
author = "{GTEx Consortium} and Fran{\c c}ois Aguet and Brown, {Andrew A.} and Castel, {Stephane E.} and Davis, {Joe R.} and Yuan He and Brian Jo and Pejman Mohammadi and Park, {Yo Son} and Princy Parsana and Segr{\`e}, {Ayellet V.} and Strober, {Benjamin J.} and Zachary Zappala and Cummings, {Beryl B.} and Gelfand, {Ellen T.} and Kane Hadley and Huang, {Katherine H.} and Monkol Lek and Xiao Li and Nedzel, {Jared L.} and Nguyen, {Duyen Y.} and Noble, {Michael S.} and Sullivan, {Timothy J.} and Taru Tukiainen and MacArthur, {Daniel G.} and Gad Getz and Anjene Addington and Ping Guan and Susan Koester and Little, {A. Roger} and Lockhart, {Nicole C.} and Moore, {Helen M.} and Abhi Rao and Struewing, {Jeffery P.} and Simona Volpi and Brigham, {Lori E.} and Richard Hasz and Marcus Hunter and Christopher Johns and Mark Johnson and Gene Kopen and Leinweber, {William F.} and Lonsdale, {John T.} and Alisa McDonald and Bernadette Mestichelli and Kevin Myer and Bryan Roe and Michael Salvatore and Saboor Shad and {Engelhardt Martin}, Barbara and Joshua Akey",
note = "Funding Information: Acknowledgements The Genotype-Tissue Expression (GTEx) project was supported by the Common Fund of the Office of the Director of the National Institutes of Health (http://commonfund.nih.gov/GTEx). 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, Inc. (Leidos) subcontracts to the National Disease Research Interchange (10XS170) and Roswell Park Cancer Institute (10XS171). The Laboratory, Data Analysis, and Coordinating Center (LDACC) was funded through a contract (HHSN268201000029C) to The Broad Institute, Inc. Biorepository operations were funded through a Leidos subcontract to the Van Andel 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. J.R.D. is supported by a Lucille P. Markey Biomedical Research Stanford Graduate Fellowship. J.R.D., Z.Z., and N.A.T. acknowledge the Stanford Genome Training Program (SGTP; NIH/NHGRI T32HG000044). Z.Z. is also supported by the National Science Foundation (NSF) GRFP (DGE-114747). L.F. is supported by the Stanford Center for Computational, Evolutionary, and Human Genomics (CEHG). D.G.M. is supported by a “la Caixa”-Severo Ochoa pre-doctoral fellowship. D.M. is supported by NIH grants U54DK105566 and R01GM104371. B.J.S is supported by NIH training grant T32GM007057. 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. T.S. is supported by a National Science Foundation Graduate Research Fellowship (DGE-1656518). A.B. is supported by the Searle Scholars Program and NIH grant R01MH109905. A.B., C.D.Bu. and S.B.M are supported by NIH grant R01HG008150 (NHGRI; Non-Coding Variants Program). S.B.M. and C.D.Bu. are supported by NHGRI grants U01HG007436 and U01HG009080. A.B., C.D.Bu., E.T.D., S.E.C., T.L, and S.B.M. are supported by NIH grants R01MH101814 (NIH Common Fund; GTEx Program). C.D.Br., Y.P., B.J., G.G., and B.E.E. are supported by NIH grant R01MH101822. B.E.E. is supported by NIH grants R00HG006265, R01MH101822 and U01 HG007900 and a Sloan Faculty Fellowship. G.L., A.B.N, J.J.P., A.S., Y-H.Z., and F.A.W. are supported by NIH grants R01MH101819, R01HG009125, and R21HG007840. T.L. and P.M. are supported by NIH grant R01MH106842. T.L. is supported by the NIH grant UM1HG008901. T.L. and S.E.C. are supported by NIH contract HHSN2682010000029C. B.J. is supported by NIH grant 2T32HG003284-11. C.B.P. and C.S. are supported by NIH grant R01MH101782. D.F.C. is supported by NIH grant R01MH101810. E.R.G and N.J.C are supported by NIH grants R01MH101820 and R01MH090937A. We thank A. Nellore and C. Wilks for assistance with TCGA data, K. Small for discussions, J. T. Leek for suggestions on the manuscript, N. L. Cyr for drawing the body map in Fig. 1a, and A. Kundaje and O. Ursu for input on Hi-C analysis. Publisher Copyright: {\textcopyright} 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.",
year = "2017",
month = oct,
day = "11",
doi = "10.1038/nature24277",
language = "English (US)",
volume = "550",
pages = "204--213",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7675",
}