Genetic effects on gene expression across human tissues View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-10-12

AUTHORS

François Aguet, Andrew A. Brown, Stephane E. Castel, Joe R. Davis, Yuan He, Brian Jo, Pejman Mohammadi, YoSon Park, Princy Parsana, Ayellet V. Segrè, Benjamin J. Strober, Zachary Zappala, Beryl B. Cummings, Ellen T. Gelfand, Kane Hadley, Katherine H. Huang, Monkol Lek, Xiao Li, Jared L. Nedzel, Duyen Y. Nguyen, Michael S. Noble, Timothy J. Sullivan, Taru Tukiainen, Daniel G. MacArthur, Gad Getz, Anjene Addington, Ping Guan, Susan Koester, A. Roger Little, Nicole C. Lockhart, Helen M. Moore, Abhi Rao, Jeffery P. Struewing, Simona Volpi, 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, Bryan 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 Valley, Deborah C. Mash, David A. Davis, Leslie Sobin, Mary E. Barcus, Philip A. Branton, Nathan S. Abell, Brunilda Balliu, Olivier Delaneau, Laure Frésard, Eric R. Gamazon, Diego Garrido-Martín, Ariel D. H. Gewirtz, Genna Gliner, Michael J. Gloudemans, Buhm Han, Amy Z. He, Farhad Hormozdiari, Xin Li, Boxiang Liu, Eun Yong Kang, Ian C. McDowell, Halit Ongen, John J. Palowitch, Christine B. Peterson, Gerald Quon, Stephan Ripke, Ashis Saha, Andrey A. Shabalin, Tyler C. Shimko, Jae Hoon Sul, Nicole A. Teran, Emily K. Tsang, Hailei Zhang, Yi-Hui Zhou, Carlos D. Bustamante, Nancy J. Cox, Roderic Guigó, Manolis Kellis, Mark I. McCarthy, Donald F. Conrad, Eleazar Eskin, Gen Li, Andrew B. Nobel, Chiara Sabatti, Barbara E. Stranger, Xiaoquan Wen, Fred A. Wright, Kristin G. Ardlie, Emmanouil T. Dermitzakis, Tuuli Lappalainen, François Aguet, Kristin G. Ardlie, Beryl B. Cummings, Ellen T. Gelfand, Gad Getz, Kane Hadley, Robert E. Handsaker, Katherine H. Huang, Seva Kashin, Konrad J. Karczewski, Monkol Lek, Xiao Li, Daniel G. MacArthur, Jared L. Nedzel, Duyen T. Nguyen, Michael S. Noble, Ayellet V. Segrè, Casandra A. Trowbridge, Taru Tukiainen, Nathan S. Abell, Brunilda Balliu, Ruth Barshir, Omer Basha, Alexis Battle, Gireesh K. Bogu, Andrew Brown, Christopher D. Brown, Stephane E. Castel, Lin S. Chen, Colby Chiang, Donald F. Conrad, Nancy J. Cox, Farhan N. Damani, Joe R. Davis, Olivier Delaneau, Emmanouil T. Dermitzakis, Barbara E. Engelhardt, Eleazar Eskin, Pedro G. Ferreira, Laure Frésard, Eric R. Gamazon, Diego Garrido-Martín, Ariel D.H. Gewirtz, Genna Gliner, Michael J. Gloudemans, Roderic Guigo, Ira M. Hall, Buhm Han, Yuan He, Farhad Hormozdiari, Cedric Howald, Hae Kyung Im, Brian Jo, Eun Yong Kang, Yungil Kim, Sarah Kim-Hellmuth, Tuuli Lappalainen, Gen Li, Xin Li, Boxiang Liu, Serghei Mangul, Mark I. McCarthy, Ian C. McDowell, Pejman Mohammadi, Jean Monlong, Stephen B. Montgomery, Manuel Muñoz-Aguirre, Anne W. Ndungu, Dan L. Nicolae, Andrew B. Nobel, Meritxell Oliva, Halit Ongen, John J. Palowitch, Nikolaos Panousis, Panagiotis Papasaikas, YoSon Park, Princy Parsana, Anthony J. Payne, Christine B. Peterson, Jie Quan, Ferran Reverter, Chiara Sabatti, Ashis Saha, Michael Sammeth, Alexandra J. Scott, Andrey A. Shabalin, Reza Sodaei, Matthew Stephens, Barbara E. Stranger, Benjamin J. Strober, Jae Hoon Sul, Emily K. Tsang, Sarah Urbut, Martijn van de Bunt, Gao Wang, Xiaoquan Wen, Fred A. Wright, Hualin S. Xi, Esti Yeger-Lotem, Zachary Zappala, Judith B. Zaugg, Yi-Hui Zhou, Joshua M. Akey, Daniel Bates, Joanne Chan, Lin S. Chen, Melina Claussnitzer, Kathryn Demanelis, Morgan Diegel, Jennifer A. Doherty, Andrew P. Feinberg, Marian S. Fernando, Jessica Halow, Kasper D. Hansen, Eric Haugen, Peter F. Hickey, Lei Hou, Farzana Jasmine, Ruiqi Jian, Lihua Jiang, Audra Johnson, Rajinder Kaul, Manolis Kellis, Muhammad G. Kibriya, Kristen Lee, Jin Billy Li, Qin Li, Xiao Li, Jessica Lin, Shin Lin, Sandra Linder, Caroline Linke, Yaping Liu, Matthew T. Maurano, Benoit Molinie, Stephen B. Montgomery, Jemma Nelson, Fidencio J. Neri, Meritxell Oliva, Yongjin Park, Brandon L. Pierce, Nicola J. Rinaldi, Lindsay F. Rizzardi, Richard Sandstrom, Andrew Skol, Kevin S. Smith, Michael P. Snyder, John Stamatoyannopoulos, Barbara E. Stranger, Hua Tang, Emily K. Tsang, Li Wang, Meng Wang, Nicholas Van Wittenberghe, Fan Wu, Rui Zhang, Concepcion R. Nierras, Philip A. Branton, Latarsha J. Carithers, Ping Guan, Helen M. Moore, Abhi Rao, Jimmie B. Vaught, Sarah E. Gould, Nicole C. Lockart, Casey Martin, Jeffery P. Struewing, Simona Volpi, Anjene M. Addington, Susan E. Koester, A. Roger Little, 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, Anita H. Undale, Anna M. Smith, David E. Tabor, Nancy V. Roche, Jeffrey A. McLean, Negin Vatanian, Karna L. Robinson, Leslie Sobin, Mary E. Barcus, Kimberly M. Valentino, Liqun Qi, Steven Hunter, Pushpa Hariharan, Shilpi Singh, Ki Sung Um, Takunda Matose, Maria M. Tomaszewski, Laura K. Barker, Maghboeba Mosavel, Laura A. Siminoff, Heather M. Traino, Paul Flicek, Thomas Juettemann, Magali Ruffier, Dan Sheppard, Kieron Taylor, Stephen J. Trevanion, Daniel R. Zerbino, Brian Craft, Mary Goldman, Maximilian Haeussler, W. James Kent, Christopher M. Lee, Benedict Paten, Kate R. Rosenbloom, John Vivian, Jingchun Zhu

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. More... »

PAGES

204-213

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  • Journal

    TITLE

    Nature

    ISSUE

    7675

    VOLUME

    550

    Author Affiliations

  • The Broad Institute of MIT and Harvard, 02142, Cambridge, Massachusetts, USA
  • Swiss Institute of Bioinformatics, 1211, Geneva, Switzerland
  • Department of Systems Biology, Columbia University, 10032, New York, New York, USA
  • Department of Pathology, Stanford University, 94305, Stanford, California, USA
  • Department of Biomedical Engineering, Johns Hopkins University, 21218, Baltimore, Maryland, USA
  • Lewis Sigler Institute, Princeton University, 08450, Princeton, New Jersey, USA
  • Department of Genetics and Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, 19104, Philadelphia, Pennsylvania, USA
  • Department of Computer Science, Johns Hopkins University, 21218, Baltimore, Maryland, USA
  • Analytic and Translational Genetics Unit, Massachusetts General Hospital, 02114, Boston, Massachusetts, USA
  • Massachusetts General Hospital Cancer Center and Department of Pathology, Massachusetts General Hospital and Harvard Medical School, 02114, Boston, Massachusetts, USA
  • Division of Neuroscience and Basic Behavioral Science, National Institute of Mental Health, 20892, Bethesda, Maryland, USA
  • Biorepositories and Biospecimen Research Branch, Cancer Diagnosis Program, National Cancer Institute, 20892, Bethesda, Maryland, USA
  • Division of Neuroscience and Behavior, National Institute on Drug Abuse, 20892, Bethesda, Maryland, USA
  • Division of Genomics and Society, National Human Genome Research Institute, 20892, Bethesda, Maryland, USA
  • Division of Genomic Medicine, National Human Genome Research Institute, 20892, Bethesda, Maryland, USA
  • Washington Regional Transplant Community, 22003, Annandale, Virginia, USA
  • Gift of Life Donor Program, 19103, Philadelphia, Pennsylvania, USA
  • LifeGift, 77055, Houston, Texas, USA
  • Center for Organ Recovery and Education, 15238, Pittsburgh, Pennsylvania, USA
  • LifeNet Health, 23453, Virginia Beach, Virginia, USA
  • National Disease Research Interchange, 19103, Philadelphia, Pennsylvania, USA
  • Unyts, 14203, Buffalo, New York, USA
  • Pharmacology and Therapeutics, Roswell Park Cancer Institute, 14263, Buffalo, New York, USA
  • Van Andel Research Institute, 49503, Grand Rapids, Michegan, USA
  • Department of Neurology, Miller School of Medicine, University of Miami, 33136, Miami, Florida, USA
  • Leidos Biomedical Research Inc., 20852, Rockville, Maryland, USA
  • Division of Genetic Medicine, Department of Medicine, Vanderbilt University, 37232, Nashville, Tennessee, USA
  • Universitat Pompeu Fabra (UPF), 08002, Barcelona, Spain
  • Department of Operations Research and Financial Engineering, Princeton University, 84540, Princeton, New Jersey, USA
  • Biomedical Informatics Program, Stanford University, 94305, Stanford, California, USA
  • Department of Convergence Medicine, University of Ulsan College of Medicine, Asan Medical Center, 05505, Seoul, Korea
  • Department of Human Genetics, University of California, 90095, Los Angeles, California, USA
  • Department of Biology, Stanford University, 94305, Stanford, California, USA
  • Department of Computer Science, University of California, 90095, Los Angeles, California, USA
  • Computational Biology and Bioinformatics Graduate Program, Duke University, 27708, Durham, North Carolina, USA
  • Department of Statistics and Operations Research, University of North Carolina, 27599, Chapel Hill, North Carolina, USA
  • Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 77030, Houston, Texas, USA
  • Computer Science and Artificial Intelligence Laboratory, MIT, 02139, Cambridge, Massachusetts, USA
  • Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, 02142, Cambridge, Massachusetts, USA
  • Center for Biomarker Research and Personalized Medicine, Virginia Commonwealth University, 23298, Richmond, Virginia, USA
  • Department of Psychiatry and Biobehavioral Sciences, University of California, 90095, Los Angeles, California, USA
  • Bioinformatics Research Center and Department of Biological Sciences, North Carolina State University, 27695, Raleigh, North Carolina, USA
  • Department of Biomedical Data Science, Stanford University, 94305, Stanford, California, USA
  • Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, OX3 7LE, Oxford, UK
  • Department of Genetics, Washington University School of Medicine, 63110, St. Louis, Missouri, USA
  • Department of Biostatistics, Mailman School of Public Health, Columbia University, 10032, New York, New York, USA
  • Department of Statistics, Stanford University, 94305, Stanford, California, USA
  • Department of Medicine, Section of Genetic Medicine, Institute for Genomics and Systems Biology, Center for Data Intensive Science, University of Chicago, 60637, Chicago, Illinois, USA
  • Department of Biostatistics, University of Michigan, 48109, Ann Arbor, Michigan, USA
  • Departments of Statistics and Biological Sciences, Bioinformatics Research Center, North Carolina State University, 27695, Raleigh, North Carolina, USA
  • The Broad Institute of Massachusetts Institute of Technology and Harvard University, 02142, Cambridge, Massachusetts, USA
  • Massachusetts General Hospital Cancer Center and Department of Pathology, Massachusetts General Hospital, 02114, Boston, Massachusetts, USA
  • Department of Genetics, Harvard Medical School, 02114, Boston, Massachusetts, USA
  • Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, 84105, Beer-Sheva, Israel
  • Department of Systems Biology, Columbia University Medical Center, 10032, New York, New York, USA
  • Department of Public Health Sciences, The University of Chicago, 60637, Chicago, Illinois, USA
  • McDonnell Genome Institute, Washington University School of Medicine, 63108, St. Louis, Missouri, USA
  • Department of Pathology & Immunology, Washington University School of Medicine, 63108, St. Louis, Missouri, USA
  • Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, 37232, Nashville, Tennessee, USA
  • Department of Computer Science and Center for Statistics and Machine Learning, Princeton University, 08540, Princeton, New Jersey, USA
  • Institute of Molecular Pathology and Immunology (IPATIMUP), University of Porto, 4200-625, Porto, Portugal
  • Department of Psychiatry, Academic Medical Center, University of Amsterdam, 1105, Amsterdam, AZ, The Netherlands
  • Lewis Sigler Institute, Princeton University, 08540, Princeton, New Jersey, USA
  • Department of Operations Research and Financial Engineering, Princeton University, 08540, Princeton, New Jersey, USA
  • Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), 08003, Barcelona, Spain
  • Department of Medicine, Washington University School of Medicine, 63108, St. Louis, Missouri, USA
  • Department of Convergence Medicine, University of Ulsan College of Medicine, Asan Medical Center, 138-736, Seoul, South Korea
  • Department of Medicine, Section of Genetic Medicine, The University of Chicago, 60637, Chicago, Illinois, USA
  • Oxford NIHR Biomedical Research Centre, Churchill Hospital, OX3 7LJ, Oxford, UK
  • Computational Biology & Bioinformatics Graduate Program, Duke University, 27708, Durham, North Carolina, USA
  • Human Genetics Department, McGill University, H3A 0G1, Montreal, Quebec, Canada
  • Departament d’Estadística i Investigació Operativa, Universitat Politècnica de Catalunya, 08034, Barcelona, Spain
  • Nuffield Department of Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, OX3 7BN, Oxford, UK
  • Department of Human Genetics, The University of Chicago, 60637, Chicago, Illinois, USA
  • Department of Biostatistics, University of North Carolina, 27599, Chapel Hill, North Carolina, USA
  • Institute for Genomics and Systems Biology, The University of Chicago, 60637, Chicago, Illinois, USA
  • Department of Genetics, Perelman School of Medicine, University of Pennsylvania, 19104, Philadelphia, Pennsylvania, USA
  • Computational Sciences, Pfizer Inc, 02139, Cambridge, Massachusetts, USA
  • Universitat de Barcelona, 08028, Barcelona, Spain
  • Institute of Biophysics Carlos Chagas Filho (IBCCF), Federal University of Rio de Janeiro (UFRJ), 21941902, Rio de Janeiro, Brazil
  • Department of Psychiatry, University of Utah, 84108, Salt Lake City, Utah, USA
  • Center for Data Intensive Science, The University of Chicago, 60637, Chicago, Illinois, USA
  • Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, OX3 7LE, Oxford, UK
  • Bioinformatics Research Center and Departments of Statistics and Biological Sciences, North Carolina State University, 27695, Raleigh, North Carolina, USA
  • National Institute for Biotechnology in the Negev, 84105, Beer-Sheva, Israel
  • European Molecular Biology Laboratory, 69117, Heidelberg, Germany
  • Department of Ecology and Evolutionary Biology, Princeton University, 08540, Princeton, New Jersey, USA
  • Altius Institute for Biomedical Sciences, 98121, Seattle, Washington, USA
  • Department of Genetics, Stanford University, 94305, Stanford, California, USA
  • University of Hohenheim, 70599, Stuttgart, Germany
  • Department of Population Health Sciences, Huntsman Cancer Institute, University of Utah, 84112, Salt Lake City, Utah, USA
  • Department of Mental Health, Johns Hopkins University School of Public Health, 21205, Baltimore, Maryland, USA
  • Department of Biostatistics, Johns Hopkins University, 21205, Baltimore, Maryland, USA
  • Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, 02139, Cambridge, Massachusetts, USA
  • Department of Medicine, University of Washington, 98195, Seattle, Washington, USA
  • Division of Cardiology, University of Washington, 98195, Seattle, Washington, USA
  • Institute for Systems Genetics, New York University Langone Medical Center, 10016, New York, New York, USA
  • Center for Epigenetics, Johns Hopkins University School of Medicine, 21205, Baltimore, Maryland, USA
  • Department of Genome Sciences, University of Washington, 98195, Seattle, Washington, USA
  • Division of Program Coordination, Office of Strategic Coordination, Planning and Strategic Initiatives, Office of the Director, NIH, 20852, Rockville, Maryland, USA
  • Division of Cancer Treatment and Diagnosis, Biorepositories and Biospecimen Research Branch, National Cancer Institute, 20892, Bethesda, Maryland, USA
  • National Institute of Dental and Craniofacial Research, 20892, Bethesda, Maryland, USA
  • Division of Genomic Medicine, National Human Genome Research Institute, 20852, Rockville, Maryland, USA
  • Division of Neuroscience and Basic Behavioral Science, National Institute of Mental Health, NIH, 20892, Bethesda, Maryland, USA
  • Division of Neuroscience and Behavior, National Institute on Drug Abuse, NIH, 20892, Bethesda, Maryland, USA
  • Washington Regional Transplant Community, 22003, Falls Church, Virginia, USA
  • LifeNet Health, Virginia Beach, 23453, Virginia, USA
  • Pharmacology and Therapeutics, Roswell Park Cancer Institute, 14263, BuffaloNew York, USA
  • Van Andel Research Institute, Grand Rapids, 49503, Michigan, USA
  • Brain Endowment Bank, Miller School of Medicine, University of Miami, 33136, Miami, Florida, USA
  • National Institute of Allergy and Infectious Diseases, NIH, 20852, Rockville, Maryland, USA
  • Biospecimen Research Group, Clinical Research Directorate, Leidos Biomedical Research, Inc., 20852, Rockville, Maryland, USA
  • Leidos Biomedical Research, Inc., 21701, Frederick, Maryland, USA
  • Temple University, 19122, Philadelphia, Pennsylvania, USA
  • Department of Health Behavior and Policy, School of Medicine, Virginia Commonwealth University, 23298, Richmond, Virginia, USA
  • European Molecular Biology Laboratory, European Bioinformatics Institute, CB10 1SD, Hinxton, UK
  • UCSC Genomics Institute, University of California Santa Cruz, 95064, Santa Cruz, California, USA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature24277

    DOI

    http://dx.doi.org/10.1038/nature24277

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1092152730

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29022597


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