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Analysis of protein-coding genetic variation in 60,706 humans

Exome Aggregation Consortium, Monkol Lek, Konrad J Karczewski, Eric V Minikel, Kaitlin E Samocha, Eric Banks, Timothy Fennell, Anne H O’Donnell-Luria, James S Ware, Andrew J Hill, Beryl B Cummings, Taru Tukiainen, Daniel P Birnbaum, Jack A Kosmicki, Laramie E Duncan, Karol Estrada, Fengmei Zhao, James Zou, Emma Pierce-Hoffman, Joanne Berghout, David N Cooper, Nicole Deflaux, Mark DePristo, Ron Do, Jason Flannick, Menachem Fromer, Laura Gauthier, Jackie Goldstein, Namrata Gupta, Daniel Howrigan, Adam Kiezun, Mitja I Kurki, Ami Levy Moonshine, Pradeep Natarajan, Lorena Orozco, Gina M Peloso, Ryan Poplin, Manuel A Rivas, Valentin Ruano-Rubio, Samuel A Rose, Douglas M Ruderfer, Khalid Shakir, Peter D Stenson, Christine Stevens, Brett P Thomas, Grace Tiao, Maria T Tusie-Luna, Ben Weisburd, Hong-Hee Won, Dongmei Yu, David M Altshuler, Diego Ardissino, Michael Boehnke, John Danesh, Stacey Donnelly, Roberto Elosua, Jose C Florez, Stacey B Gabriel, Gad Getz, Stephen J Glatt, Christina M Hultman, Sekar Kathiresan, Markku Laakso, Steven McCarroll, Mark I McCarthy, Dermot McGovern, Ruth McPherson, Benjamin M Neale, Aarno Palotie, Shaun M Purcell, Danish Saleheen, Jeremiah M Scharf, Pamela Sklar, Patrick F Sullivan, Jaakko Tuomilehto, Ming T Tsuang, Hugh C Watkins, James G Wilson, Mark J Daly, Daniel G MacArthur
doi: https://doi.org/10.1101/030338
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
Monkol Lek
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USAProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USASchool of Paediatrics and Child Health, University of Sydney, Sydney, NSW, AustraliaInstitute for Neuroscience and Muscle Research, Childrens Hospital at Westmead, Sydney, NSW, Australia
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Konrad J Karczewski
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USAProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Eric V Minikel
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USAProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USAProgram in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA, USA
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Kaitlin E Samocha
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USAProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USAProgram in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA, USAStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Eric Banks
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Timothy Fennell
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Anne H O’Donnell-Luria
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USAProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USADivision of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA
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James S Ware
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USADepartment of Genetics, Harvard Medical School, Boston, MA, USANational Heart and Lung Institute, Imperial College London, London, UKNIHR Royal Brompton Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, UKMRC Clinical Sciences Centre, Imperial College London, London, UK
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Andrew J Hill
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USAProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USAGenome Sciences, University of Washington, Seattle, WA, USA
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Beryl B Cummings
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USAProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USAProgram in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA, USA
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Taru Tukiainen
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USAProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Daniel P Birnbaum
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Jack A Kosmicki
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USAProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USAStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USAProgram in Bioinformatics and Integrative Genomics, Harvard Medical School, Boston, MA, USA
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Laramie E Duncan
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USAProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USAStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Karol Estrada
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USAProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Fengmei Zhao
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USAProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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James Zou
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Emma Pierce-Hoffman
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USAProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Joanne Berghout
Mouse Genome Informatics, Jackson Laboratory, Bar Harbor, ME, USACenter for Biomedical Informatics and Biostatistics, University of Arizona, Tucson, AZ, USA
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David N Cooper
Institute of Medical Genetics, Cardiff University, Cardiff, UK
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Nicole Deflaux
Google Inc, Mountain View, CA, USA
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Mark DePristo
Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Ron Do
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USAInstitute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USAThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USAThe Center for Statistical Genetics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Jason Flannick
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USAProgram in Bioinformatics and Integrative Genomics, Harvard Medical School, Boston, MA, USA
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Menachem Fromer
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USAStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USADepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USADepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USAInstitute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Laura Gauthier
Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Jackie Goldstein
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USAProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USAStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Namrata Gupta
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Daniel Howrigan
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USAProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USAStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Adam Kiezun
Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Mitja I Kurki
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USAPsychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
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Ami Levy Moonshine
Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Pradeep Natarajan
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USAHarvard Medical School, Boston, MA, USACenter for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USACardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA
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Lorena Orozco
Immunogenomics and Metabolic Disease Laboratory, Instituto Nacional de Medicina Gen—mica, Mexico City, Mexico
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Gina M Peloso
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USACenter for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USACardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA
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Ryan Poplin
Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Manuel A Rivas
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Valentin Ruano-Rubio
Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Samuel A Rose
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Douglas M Ruderfer
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USADepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USAInstitute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Khalid Shakir
Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Peter D Stenson
Institute of Medical Genetics, Cardiff University, Cardiff, UK
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Christine Stevens
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Brett P Thomas
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USAProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Grace Tiao
Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Maria T Tusie-Luna
Molecular Biology and Genomic Medicine Unit, Instituto Nacional de Ciencias M_dicas y Nutrici—n, Mexico City, Mexico
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Ben Weisburd
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Hong-Hee Won
Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University,Samsung Medical Center, Seoul, Republic of Korea
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Dongmei Yu
Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA, USACenter for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USAPsychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USADepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA
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David M Altshuler
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USAVertex Pharmaceuticals, Boston, MA, USA
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Diego Ardissino
Department of Cardiology, University Hospital, Parma, Italy
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Michael Boehnke
Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA
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John Danesh
Department of Public Health and Primary Care, Strangeways Research Laboratory, Cambridge, UK
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Stacey Donnelly
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Roberto Elosua
Cardiovascular Epidemiology and Genetics, Hospital del Mar Medical Research Institute, Barcelona, Spain
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Jose C Florez
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USAHarvard Medical School, Boston, MA, USACenter for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA
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Stacey B Gabriel
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Gad Getz
Broad Institute of MIT and Harvard, Cambridge, MA, USAHarvard Medical School, Boston, MA, USADepartment of Pathology and Cancer Center, Massachusetts General Hospital, Boston, MA, USA
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Stephen J Glatt
Psychiatric Genetic Epidemiology & Neurobiology Laboratory, State University of New York,Upstate Medical University, Syracuse, NY, USADepartment of Psychiatry and Behavioral Sciences, State University of New York, Upstate Medical University, Syracuse, NY, USADepartment of Neuroscience and Physiology, State University of New York,Upstate Medical University, Syracuse, NY, USA
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Christina M Hultman
Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
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Sekar Kathiresan
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USAHarvard Medical School, Boston, MA, USACenter for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USACardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA
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Markku Laakso
Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
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Steven McCarroll
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USADepartment of Genetics, Harvard Medical School, Boston, MA, USA
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Mark I McCarthy
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UKOxford Centre for Diabetes,Endocrinology and Metabolism, University of Oxford, Oxford, UKOxford NIHR Biomedical Research Centre, Oxford University Hospitals Foundation Trust, Oxford, UK
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Dermot McGovern
Inflammatory Bowel Disease and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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Ruth McPherson
Atherogenomics Laboratory, University of Ottawa Heart Institute, Ottawa, ON, Canada
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Benjamin M Neale
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USAProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USAStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Aarno Palotie
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USAProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USAProgram in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA, USAInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
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Shaun M Purcell
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USADepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USAInstitute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Danish Saleheen
Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USADepartment of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USACenter for Non-Communicable Diseases, Karachi, Pakistan
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Jeremiah M Scharf
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USAStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USACenter for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USAPsychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USADepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA
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Pamela Sklar
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USADepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USAInstitute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USAFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USADepartment of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Patrick F Sullivan
Department of Genetics, University of North Carolina, Chapel Hill, NC, USADepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
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Jaakko Tuomilehto
Department of Public Health, University of Helsinki, Helsinki, Finland
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Ming T Tsuang
Department of Psychiatry, University of California, San Diego, CA, USA
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Hugh C Watkins
Radcliffe Department of Medicine, University of Oxford, Oxford, UKWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
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James G Wilson
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA
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Mark J Daly
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USAProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USAStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Daniel G MacArthur
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USAProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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  • Abstract
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Summary

Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) sequence data for 60,706 individuals of diverse ethnicities generated as part of the Exome Aggregation Consortium (ExAC). The resulting catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We show that this catalogue can be used to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; we identify 3,230 genes with near-complete depletion of truncating variants, 72% of which have no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human “knockout” variants in protein-coding genes.

Footnotes

  • ↵# List of collaborators to appear at the end of manuscript

  • ↵61 Department of Medicine, University of Texas Health Science Center, San Antonio, TX, USA

  • ↵62 Instituto Nacional de Ciencias M_dicas y Nutrici—n Salvador Zubir‡n, Mexico City, Mexico

  • ↵63 Departments of Medicine and Genetics, Albert Einstein College of Medicine, New York City, NY, USA

  • ↵64 Department of Natural Science, University of Haifa, Haifa, Israel

  • ↵65 Department of Clinical Science, University of Bergen, Bergen, Norway

  • ↵66 Department of Pediatrics, Haukeland University Hospital, Bergen, Norway

  • ↵67 Department of Biomedicine, University of Bergen, Bergen, Norway

  • ↵68 The Toronto Western Research Institute, University Health Network, Toronto, Canada

  • ↵69 The Hospital for Sick Children, Toronto, Canada

  • ↵70 Departments of Medicine and Human Genetics, University of Chicago, Chicago, IL, USA

  • ↵71 Department of Medicine, University of Chicago, Chicago, IL, USA

  • ↵72 South Texas Diabetes and Obesity Institute, University of Texas Health Science Center, San Antonio, TX, USA

  • ↵73 University of Texas Rio Grande Valley, Brownsville, TX, USA

  • ↵74 Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA

  • ↵75 Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA

  • ↵76 Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA

  • ↵77 North Shore-Long Island Jewish Health System, Manhasset, NY, USA

  • ↵78 Instituto Nacional de Medicina Gen—mica, Mexico City, Mexico

  • ↵79 Department of Epidemiology and Biostatistics, Imperial College London, London, UK

  • ↵80 Department of Cardiology, Ealing Hospital NHS Trust, Southall, UK

  • ↵81 Imperial College Healthcare NHS Trust, Imperial College London, London, UK

  • ↵82 Nuffield Department of Population Health, University of Oxford, Oxford, UK

  • ↵83 Center for Neurobehavioral Genetics, University of California, Los Angeles, CA, USA

  • ↵84 Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, TN, USA

  • ↵85 Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA

  • ↵86 University of Exeter Medical School, University of Exeter, Exeter, UK

  • ↵87 Instituto Nacional de Salud Publica, Mexico City, Mexico

  • ↵88 Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA

  • ↵89 Department of Clinical Sciences, Lund University Diabetes Centre, Malm_, Sweden

  • ↵90 Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA

  • ↵91 Human Genetics Center, The University of Texas Health Science Center, Houston, TX, USA

  • ↵92 Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA

  • ↵93 Instituto de Investigaciones Biom_dicas, Mexico City, Mexico

  • ↵94 Instituto Mexicano del Seguro Social, Mexico City, Mexico

  • ↵95 Department of Genetics, Yale University School of Medicine, New Haven, CT, USA

  • ↵96 MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK

  • ↵97 Center for Genome Science, Korea National Institute of Health, Chungcheongbuk-do, Republic of Korea

  • ↵98 Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Woodbury, NY, USA

  • ↵99 Department of Psychiatry, University of Utah, Salt Lake City, UT, USA

  • ↵100 Nuffield Department of Medicine, University of Oxford, Oxford, UK

  • ↵101 Department of Psychiatry, University of Florida, Gainesville, FL, USA

  • ↵102 General Medicine Division, Massachusetts General Hospital, Boston, MA, USA

  • ↵103 Institute of Human Genetics, Technische Universit_t MŸnchen, Munich, Germany

  • ↵104 Institute of Human Genetics, German Research Center for Environmental Health, Neuherberg, Germany

  • ↵105 Diabetes Research Center (Diabetes Unit), Massachusetts General Hospital, Boston, MA, USA

  • ↵106 Research Program in Computational Biology, Barcelona Supercomputing Center, Barcelona, Spain

  • ↵107 Universidad Aut—noma Metropolitana, Mexico City, Mexico

  • ↵108 Estonian Genome Centre,University of Tartu,Tartu,Estonia, University of Tartu, Tartu, Estonia

  • ↵109 Department of Biostatistics, University of Liverpool, Liverpool, UK

  • ↵110 Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway

  • ↵111 Interdisoiplinary Program in Bioinformatics, Seoul National University, Seoul, Republic of Korea

  • ↵112 Department of Statistics, Seoul National University, Seoul, Republic of Korea

  • ↵113 Department of Functional Genomics, University of Amsterdam, Amsterdam, The Netherlands

  • ↵114 Department of Clinical Genetics, VU Medical Centre, Amsterdam, The Netherlands

  • ↵115 Department of Child and Adolescent Psychiatry, Erasmus University Medical Centre, Rotterdam, The Netherlands

  • ↵116 Department of Psychiatry, University of Toronto, Toronto, Canada

  • ↵117 Department of Laboratory Medicine, University of California, San Francisco, CA, USA

  • ↵118 Blood Systems Research Institute, San Francisco, CA, USA

  • ↵119 Department of Human Genetics, McGill University, Montreal, Canada

  • ↵120 Department of Medicine, McGill University, Montreal, Canada

  • ↵121 McGill University and G_nome Qu_bec Innovation Centre, Montreal, Canada

  • ↵122 Department of Twin Research and Genetic Epidemiology, King's College London, London, UK

  • ↵123 Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore

  • ↵124 Department of Medicine, National University of Singapore, Singapore, Singapore

  • ↵125 Cardiovascular & Metabolic Disorders Program, Duke-NUS Graduate Medical School Singapore, Singapore, Singapore

  • ↵126 Department of Biological Sciences, Columbia University, New York, NY, USA

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Analysis of protein-coding genetic variation in 60,706 humans
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Analysis of protein-coding genetic variation in 60,706 humans
Exome Aggregation Consortium, Monkol Lek, Konrad J Karczewski, Eric V Minikel, Kaitlin E Samocha, Eric Banks, Timothy Fennell, Anne H O’Donnell-Luria, James S Ware, Andrew J Hill, Beryl B Cummings, Taru Tukiainen, Daniel P Birnbaum, Jack A Kosmicki, Laramie E Duncan, Karol Estrada, Fengmei Zhao, James Zou, Emma Pierce-Hoffman, Joanne Berghout, David N Cooper, Nicole Deflaux, Mark DePristo, Ron Do, Jason Flannick, Menachem Fromer, Laura Gauthier, Jackie Goldstein, Namrata Gupta, Daniel Howrigan, Adam Kiezun, Mitja I Kurki, Ami Levy Moonshine, Pradeep Natarajan, Lorena Orozco, Gina M Peloso, Ryan Poplin, Manuel A Rivas, Valentin Ruano-Rubio, Samuel A Rose, Douglas M Ruderfer, Khalid Shakir, Peter D Stenson, Christine Stevens, Brett P Thomas, Grace Tiao, Maria T Tusie-Luna, Ben Weisburd, Hong-Hee Won, Dongmei Yu, David M Altshuler, Diego Ardissino, Michael Boehnke, John Danesh, Stacey Donnelly, Roberto Elosua, Jose C Florez, Stacey B Gabriel, Gad Getz, Stephen J Glatt, Christina M Hultman, Sekar Kathiresan, Markku Laakso, Steven McCarroll, Mark I McCarthy, Dermot McGovern, Ruth McPherson, Benjamin M Neale, Aarno Palotie, Shaun M Purcell, Danish Saleheen, Jeremiah M Scharf, Pamela Sklar, Patrick F Sullivan, Jaakko Tuomilehto, Ming T Tsuang, Hugh C Watkins, James G Wilson, Mark J Daly, Daniel G MacArthur
bioRxiv 030338; doi: https://doi.org/10.1101/030338
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Analysis of protein-coding genetic variation in 60,706 humans
Exome Aggregation Consortium, Monkol Lek, Konrad J Karczewski, Eric V Minikel, Kaitlin E Samocha, Eric Banks, Timothy Fennell, Anne H O’Donnell-Luria, James S Ware, Andrew J Hill, Beryl B Cummings, Taru Tukiainen, Daniel P Birnbaum, Jack A Kosmicki, Laramie E Duncan, Karol Estrada, Fengmei Zhao, James Zou, Emma Pierce-Hoffman, Joanne Berghout, David N Cooper, Nicole Deflaux, Mark DePristo, Ron Do, Jason Flannick, Menachem Fromer, Laura Gauthier, Jackie Goldstein, Namrata Gupta, Daniel Howrigan, Adam Kiezun, Mitja I Kurki, Ami Levy Moonshine, Pradeep Natarajan, Lorena Orozco, Gina M Peloso, Ryan Poplin, Manuel A Rivas, Valentin Ruano-Rubio, Samuel A Rose, Douglas M Ruderfer, Khalid Shakir, Peter D Stenson, Christine Stevens, Brett P Thomas, Grace Tiao, Maria T Tusie-Luna, Ben Weisburd, Hong-Hee Won, Dongmei Yu, David M Altshuler, Diego Ardissino, Michael Boehnke, John Danesh, Stacey Donnelly, Roberto Elosua, Jose C Florez, Stacey B Gabriel, Gad Getz, Stephen J Glatt, Christina M Hultman, Sekar Kathiresan, Markku Laakso, Steven McCarroll, Mark I McCarthy, Dermot McGovern, Ruth McPherson, Benjamin M Neale, Aarno Palotie, Shaun M Purcell, Danish Saleheen, Jeremiah M Scharf, Pamela Sklar, Patrick F Sullivan, Jaakko Tuomilehto, Ming T Tsuang, Hugh C Watkins, James G Wilson, Mark J Daly, Daniel G MacArthur
bioRxiv 030338; doi: https://doi.org/10.1101/030338

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