Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-02-10

AUTHORS

Daniel Taliun, Daniel N. Harris, Michael D. Kessler, Jedidiah Carlson, Zachary A. Szpiech, Raul Torres, Sarah A. Gagliano Taliun, André Corvelo, Stephanie M. Gogarten, Hyun Min Kang, Achilleas N. Pitsillides, Jonathon LeFaive, Seung-been Lee, Xiaowen Tian, Brian L. Browning, Sayantan Das, Anne-Katrin Emde, Wayne E. Clarke, Douglas P. Loesch, Amol C. Shetty, Thomas W. Blackwell, Albert V. Smith, Quenna Wong, Xiaoming Liu, Matthew P. Conomos, Dean M. Bobo, François Aguet, Christine Albert, Alvaro Alonso, Kristin G. Ardlie, Dan E. Arking, Stella Aslibekyan, Paul L. Auer, John Barnard, R. Graham Barr, Lucas Barwick, Lewis C. Becker, Rebecca L. Beer, Emelia J. Benjamin, Lawrence F. Bielak, John Blangero, Michael Boehnke, Donald W. Bowden, Jennifer A. Brody, Esteban G. Burchard, Brian E. Cade, James F. Casella, Brandon Chalazan, Daniel I. Chasman, Yii-Der Ida Chen, Michael H. Cho, Seung Hoan Choi, Mina K. Chung, Clary B. Clish, Adolfo Correa, Joanne E. Curran, Brian Custer, Dawood Darbar, Michelle Daya, Mariza de Andrade, Dawn L. DeMeo, Susan K. Dutcher, Patrick T. Ellinor, Leslie S. Emery, Celeste Eng, Diane Fatkin, Tasha Fingerlin, Lukas Forer, Myriam Fornage, Nora Franceschini, Christian Fuchsberger, Stephanie M. Fullerton, Soren Germer, Mark T. Gladwin, Daniel J. Gottlieb, Xiuqing Guo, Michael E. Hall, Jiang He, Nancy L. Heard-Costa, Susan R. Heckbert, Marguerite R. Irvin, Jill M. Johnsen, Andrew D. Johnson, Robert Kaplan, Sharon L. R. Kardia, Tanika Kelly, Shannon Kelly, Eimear E. Kenny, Douglas P. Kiel, Robert Klemmer, Barbara A. Konkle, Charles Kooperberg, Anna Köttgen, Leslie A. Lange, Jessica Lasky-Su, Daniel Levy, Xihong Lin, Keng-Han Lin, Chunyu Liu, Ruth J. F. Loos, Lori Garman, Robert Gerszten, Steven A. Lubitz, Kathryn L. Lunetta, Angel C. Y. Mak, Ani Manichaikul, Alisa K. Manning, Rasika A. Mathias, David D. McManus, Stephen T. McGarvey, James B. Meigs, Deborah A. Meyers, Julie L. Mikulla, Mollie A. Minear, Braxton D. Mitchell, Sanghamitra Mohanty, May E. Montasser, Courtney Montgomery, Alanna C. Morrison, Joanne M. Murabito, Andrea Natale, Pradeep Natarajan, Sarah C. Nelson, Kari E. North, Jeffrey R. O’Connell, Nicholette D. Palmer, Nathan Pankratz, Gina M. Peloso, Patricia A. Peyser, Jacob Pleiness, Wendy S. Post, Bruce M. Psaty, D. C. Rao, Susan Redline, Alexander P. Reiner, Dan Roden, Jerome I. Rotter, Ingo Ruczinski, Chloé Sarnowski, Sebastian Schoenherr, David A. Schwartz, Jeong-Sun Seo, Sudha Seshadri, Vivien A. Sheehan, Wayne H. Sheu, M. Benjamin Shoemaker, Nicholas L. Smith, Jennifer A. Smith, Nona Sotoodehnia, Adrienne M. Stilp, Weihong Tang, Kent D. Taylor, Marilyn Telen, Timothy A. Thornton, Russell P. Tracy, David J. Van Den Berg, Ramachandran S. Vasan, Karine A. Viaud-Martinez, Scott Vrieze, Daniel E. Weeks, Bruce S. Weir, Scott T. Weiss, Lu-Chen Weng, Cristen J. Willer, Yingze Zhang, Xutong Zhao, Donna K. Arnett, Allison E. Ashley-Koch, Kathleen C. Barnes, Eric Boerwinkle, Stacey Gabriel, Richard Gibbs, Kenneth M. Rice, Stephen S. Rich, Edwin K. Silverman, Pankaj Qasba, Weiniu Gan, George J. Papanicolaou, Deborah A. Nickerson, Sharon R. Browning, Michael C. Zody, Sebastian Zöllner, James G. Wilson, L. Adrienne Cupples, Cathy C. Laurie, Cashell E. Jaquish, Ryan D. Hernandez, Timothy D. O’Connor, Gonçalo R. Abecasis

ABSTRACT

The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases. The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here we describe the TOPMed goals and design as well as the available resources and early insights obtained from the sequence data. The resources include a variant browser, a genotype imputation server, and genomic and phenotypic data that are available through dbGaP (Database of Genotypes and Phenotypes)1. In the first 53,831 TOPMed samples, we detected more than 400 million single-nucleotide and insertion or deletion variants after alignment with the reference genome. Additional previously undescribed variants were detected through assembly of unmapped reads and customized analysis in highly variable loci. Among the more than 400 million detected variants, 97% have frequencies of less than 1% and 46% are singletons that are present in only one individual (53% among unrelated individuals). These rare variants provide insights into mutational processes and recent human evolutionary history. The extensive catalogue of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and noncoding sequence variants to phenotypic variation. Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and reach of genome-wide association studies to include variants down to a frequency of approximately 0.01%. More... »

PAGES

290-299

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  • Journal

    TITLE

    Nature

    ISSUE

    7845

    VOLUME

    590

    Author Affiliations

  • Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA
  • Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
  • Department of Genome Sciences, University of Washington, Seattle, WA, USA
  • Institute for Computational and Data Sciences, Pennsylvania State University, University Park, PA, USA
  • Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, USA
  • New York Genome Center, New York, NY, USA
  • Department of Biostatistics, University of Washington, Seattle, WA, USA
  • Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
  • Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, WA, USA
  • USF Genomics, College of Public Health, University of South Florida, Tampa, FL, USA
  • Icahn School of Medicine at Mount Sinai, New York, NY, USA
  • The Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Massachusetts General Hospital, Boston, MA, USA
  • Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA
  • McKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
  • University of Alabama, Birmingham, AL, USA
  • Zilber School of Public Health, University of Wisconsin Milwaukee, Milwaukee, WI, USA
  • Cleveland Clinic, Cleveland, OH, USA
  • Department of Epidemiology, Columbia University Medical Center, New York, NY, USA
  • The Emmes Corporation, Rockville, MD, USA
  • Johns Hopkins University, Baltimore, MD, USA
  • National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
  • Framingham Heart Study, Framingham, MA, USA
  • Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA
  • South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA
  • Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA
  • Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA
  • Department of Medicine, University of California, San Francisco, San Francisco, CA, USA
  • Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
  • Division of Pediatric Hematology, Johns Hopkins University, Baltimore, MD, USA
  • Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada
  • Harvard Medical School, Boston, MA, USA
  • The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation, Harbor-UCLA Medical Center, Torrance, CA, USA
  • Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
  • Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, USA
  • Metabolomics Platform, The Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Department of Population Health Science, University of Mississippi Medical Center, Jackson, MS, USA
  • Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA
  • Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA
  • Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
  • Mayo Clinic, Rochester, MN, USA
  • Department of Genetics, Washington University, St Louis, MO, USA
  • Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Cardiology Department, St Vincent’s Hospital, Darlinghurst, New South Wales, Australia
  • National Jewish Health, Center for Genes, Environment and Health, Denver, CO, USA
  • Institute of Genetic Epidemiology, Department of Genetics and Pharmacology, Medical University of Innsbruck, Innsbruck, Austria
  • Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA
  • Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA
  • Institute for Biomedicine, Eurac Research, Bolzano, Italy
  • Department of Bioethics & Humanities, University of Washington School of Medicine, Seattle, WA, USA
  • Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
  • Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, Boston, MA, USA
  • Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA
  • Tulane University Translational Science Institute, Tulane University, New Orleans, LA, USA
  • Department of Neurology, Boston University School of Medicine, Boston, MA, USA
  • Department of Epidemiology, University of Washington, Seattle, WA, USA
  • Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA
  • Bloodworks Northwest Research Institute, Seattle, WA, USA
  • Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Framingham, MA, USA
  • Albert Einstein College of Medicine, New York, NY, USA
  • Department of Epidemiology, Tulane University, New Orleans, LA, USA
  • Division of Pediatric Hematology, UCSF Benioff Children’s Hospital, Oakland, CA, USA
  • Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
  • Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  • Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
  • Department of Medicine, University of Colorado at Denver, Aurora, CO, USA
  • Brigham and Women’s Hospital, Boston, MA, USA
  • Biostatistics and Statistics, Harvard University, Boston, MA, USA
  • The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  • Department of Genes and Human Disease, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
  • Beth Israel Deaconess Medical Center, Boston, MA, USA
  • Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA
  • Metabolism Program, The Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Department of Medicine, Johns Hopkins University, Baltimore, MD, USA
  • Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, MA, USA
  • Department of Anthropology, Brown University, Providence, RI, USA
  • Division of General Internal Medicine, Massachusetts General Hospital, Harvard Medical School, The Broad Institute of MIT and Harvard, Boston, MA, USA
  • University of Arizona, Tucson, AZ, USA
  • Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, MD, USA
  • Department of Internal Medicine, Dell Medical School, Austin, TX, USA
  • Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA
  • Department of Medicine, Boston University School of Medicine, Boston, MA, USA
  • Texas Cardiac Arrhythmia Institute, St David’s Medical Center, Austin, TX, USA
  • Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA
  • Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
  • Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA
  • Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA
  • Division of Biostatistics, Washington University in St Louis, St Louis, MO, USA
  • Vanderbilt University Medical Center, Nashville, TN, USA
  • Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
  • University of Colorado at Denver, Denver, CO, USA
  • Gong Wu Genomic Medicine Institute, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
  • Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, University of Texas Health Sciences Center at San Antonio, San Antonio, TX, USA
  • Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta, Atlanta, GA, USA
  • Taichung Veterans General Hospital Taiwan, Taichung City, Taiwan
  • Seattle Epidemiologic Research and Information Center, Department of Veterans Affairs Office of Research and Development, Seattle, WA, USA
  • Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA
  • Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA
  • Duke University, Durham, NC, USA
  • Department of Pathology & Laboratory Medicine, University of Vermont Larner College of Medicine, Burlington, VT, USA
  • Center for Genetic Epidemiology, Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA
  • Illumina Laboratory Services, Illumina Inc, San Diego, CA, USA
  • Department of Psychology, University of Minnesota, Minneapolis, MN, USA
  • Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
  • Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA
  • Department of Epidemiology, University of Kentucky, Lexington, KY, USA
  • Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA
  • Baylor College of Medicine Human Genome Sequencing Center, Houston, TX, USA
  • Brotman Baty Institute, Seattle, WA, USA
  • Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA
  • Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA
  • Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA
  • Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41586-021-03205-y

    DOI

    http://dx.doi.org/10.1038/s41586-021-03205-y

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1135304303

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/33568819


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