New Results
Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program
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, Quenna Wong, François Aguet, Christine Albert, Alvaro Alonso, Kristin G. Ardlie, Stella Aslibekyan, Paul L. Auer, John Barnard, R. Graham Barr, 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, 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, Diane Fatkin, 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, 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 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, 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, Jeong-Sun Seo, Sudha Seshadri, Vivien A. Sheehan, M. Benjamin Shoemaker, Albert V. Smith, 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 Silverman, Pankaj Qasba, Weiniu Gan, Trans-Omics for Precision Medicine (TOPMed) Program, TOPMed Population Genetics Working Group, 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
doi: https://doi.org/10.1101/563866
Daniel Taliun
Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI;
Daniel N. Harris
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD;Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD;Department of Medicine, University of Maryland School of Medicine, Baltimore, MD;
Michael D. Kessler
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD;Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD;Department of Medicine, University of Maryland School of Medicine, Baltimore, MD;
Jedidiah Carlson
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI;Department of Genome Sciences, University of Washington, Seattle, WA;
Zachary A. Szpiech
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA;Department of Biological Sciences, Auburn University, Auburn, AL;
Raul Torres
Biomedical Sciences Graduate Program, University of California, San Francisco, CA;
Sarah A. Gagliano Taliun
Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI;
André Corvelo
New York Genome Center, New York, NY;
Stephanie M. Gogarten
Department of Biostatistics, University of Washington, Seattle, WA;
Hyun Min Kang
Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI;
Achilleas N. Pitsillides
Department of Biostatistics, Boston University School of Public Health, Boston, MA;
Jonathon LeFaive
Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI;
Seung-been Lee
Department of Genome Sciences, University of Washington, Seattle, WA;
Xiaowen Tian
Department of Biostatistics, University of Washington, Seattle, WA;
Brian L. Browning
Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, WA;
Sayantan Das
Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI;
Anne-Katrin Emde
New York Genome Center, New York, NY;
Wayne E. Clarke
New York Genome Center, New York, NY;
Douglas P. Loesch
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD;Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD;Department of Medicine, University of Maryland School of Medicine, Baltimore, MD;
Amol C. Shetty
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD;Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD;Department of Medicine, University of Maryland School of Medicine, Baltimore, MD;
Thomas W. Blackwell
Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI;
Quenna Wong
Department of Biostatistics, University of Washington, Seattle, WA;
François Aguet
The Broad Institute of MIT and Harvard, Cambridge, MA;
Christine Albert
Massachusetts General Hospital, Boston, MA;
Alvaro Alonso
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA;
Kristin G. Ardlie
The Broad Institute of MIT and Harvard, Cambridge, MA;
Stella Aslibekyan
University of Alabama, Birmingham, AL;
Paul L. Auer
Zilber School of Public Health, University of Wisconsin Milwaukee, Milwaukee, WI;
John Barnard
Cleveland Clinic, Cleveland, OH;
R. Graham Barr
Department of Medicine, Columbia University Medical Center, New York, NY;Department of Epidemiology, Columbia University Medical Center, New York, NY;
Lewis C. Becker
Johns Hopkins University, Baltimore, MD;
Rebecca L. Beer
National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;
Emelia J. Benjamin
Department of Medicine, Boston University School of Medicine, Boston, MA;Department of Epidemiology, Boston University School of Public Health, Boston, MA;Framingham Heart Study, Framingham, MA;
Lawrence F. Bielak
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI;
John Blangero
Department of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX;South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX;
Michael Boehnke
Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI;
Donald W. Bowden
Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC;
Jennifer A. Brody
Department of Medicine, University of Washington, Seattle, WA;Cardiovascular Health Research Unit, University of Washington, Seattle, WA;
Esteban G. Burchard
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA;Department of Medicine, University of California, San Francisco, CA;
Brian E. Cade
Department of Medicine, Harvard Medical School, Boston, MA;Department of Medicine, Brigham and Women’s Hospital, Boston, MA;
James F. Casella
Department of Pediatrics, Johns Hopkins University, Baltimore, MD;Division of Pediatric Hematology, Johns Hopkins University, Baltimore, MD;
Brandon Chalazan
Department of Medical Genetics, University of British Columbia, Vancouver, BC;
Yii-Der Ida Chen
Department of Pediatrics, The Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA;
Michael H. Cho
Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA;
Seung Hoan Choi
The Broad Institute of MIT and Harvard, Cambridge, MA;
Mina K. Chung
Department of Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, Cleveland, Ohio, USA;Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA;Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA;
Clary B. Clish
Metabolomics Platform, The Broad Institute of MIT and Harvard, Cambridge, MA;
Adolfo Correa
Department of Medicine, University of Mississippi Medical Center, Jackson, MS;Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS;Department of Population Health Science, University of Mississippi Medical Center, Jackson, MS;
Joanne E. Curran
Department of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX;South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX;
Brian Custer
Vitalant Research Institute, San Francisco, CA, USA;Department of Laboratory Medicine, UCSF, San Francisco, CA, USA;
Dawood Darbar
Department of Medicine, University of Illinois at Chicago, Chicago, IL;
Michelle Daya
School of Medicine, University of Colorado, Aurora, CO;
Mariza de Andrade
Mayo Clinic, Rochester, MN;
Dawn L. DeMeo
Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA;
Susan K. Dutcher
McDonnell Genome Institute and Department of Genetics, Washington University, St Louis, MO;
Patrick T. Ellinor
Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA;
Leslie S. Emery
Department of Biostatistics, University of Washington, Seattle, WA;
Diane Fatkin
Molecular Cardiology Division, Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia;Faculty of Medicine, University of New South Wales, Kensington, NSW, Australia;Cardiology Department, St. Vincent’s Hospital, Darlinghurst, NSW, Australia;
Lukas Forer
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria;
Myriam Fornage
Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX;
Nora Franceschini
Department of Epidemiology, University of North Carolina, Chapel Hill, NC;
Christian Fuchsberger
Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI;Institute for Biomedicine, Eurac Research, Bolzano, Italy;
Stephanie M. Fullerton
Department of Bioethics & Humanities, University of Washington School of Medicine, Seattle, WA;
Soren Germer
New York Genome Center, New York, NY;
Mark T. Gladwin
Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA;Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA;Department of Medicine, University of Pittsburgh, Pittsburgh, PA;
Daniel J. Gottlieb
VA Boston Healthcare System, Boston, MA;Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, Boston, MA;
Xiuqing Guo
Department of Pediatrics, The Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA;
Michael E. Hall
Department of Medicine, University of Mississippi Medical Center, Jackson, MS;
Jiang He
Department of Epidemiology, Tulane University, New Orleans, LA;Tulane University Translational Science Institute, Tulane University, New Orleans, LA;
Nancy L. Heard-Costa
Framingham Heart Study, Framingham, MA;Department of Neurology, Boston University School of Medicine, Boston, MA;
Susan R. Heckbert
Cardiovascular Health Research Unit, University of Washington, Seattle, WA;Department of Epidemiology, University of Washington, Seattle, WA;
Marguerite R. Irvin
Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL;
Jill M. Johnsen
Department of Medicine, University of Washington, Seattle, WA;Bloodworks Northwest Research Institute, Seattle, WA;
Andrew D. Johnson
Framingham Heart Study, Framingham, MA;Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Framingham, MA;
Sharon L.R. Kardia
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI;
Tanika Kelly
Department of Epidemiology, Tulane University, New Orleans, LA;
Shannon Kelly
Department of Epidemiology, Vitalant Research Institute, San Francisco, CA;Department of Pediatrics, UCSF Benioff Children’s Hospital, Oakland, CA;Division of Pediatric Hematology, UCSF Benioff Children’s Hospital, Oakland, CA;
Eimear E. Kenny
Icahn School of Medicine at Mount Sinai, New York, NY;
Douglas P. Kiel
Department of Medicine, Harvard Medical School, Boston, MA;Marcus Institute for Aging Research/Harvard Medical School, Hebrew SeniorLife, Boston, MA;Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA;
Robert Klemmer
Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI;
Barbara A. Konkle
Department of Medicine, University of Washington, Seattle, WA;Bloodworks Northwest Research Institute, Seattle, WA;
Charles Kooperberg
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA;
Anna Köttgen
Department of Epidemiology, Johns Hopkins University, Baltimore, MD;Institute of Genetic Epidemiology, Medical Center - University of Freiburg, Freiburg, Germany;
Leslie A. Lange
Department of Medicine, University of Colorado at Denver, Aurora, CO;
Jessica Lasky-Su
Department of Medicine, Harvard Medical School, Boston, MA;Department of Medicine, Brigham and Women’s Hospital, Boston, MA;Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA;Brigham and Women’s Hospital, Boston, MA;
Daniel Levy
Department of Medicine, Boston University School of Medicine, Boston, MA;Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Framingham, MA;
Xihong Lin
Biostatistics and Statistics, Harvard University, Boston, MA;
Keng-Han Lin
Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI;
Chunyu Liu
Department of Biostatistics, Boston University School of Public Health, Boston, MA;
Ruth J.F. Loos
The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA;The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA;
Lori Garman
Division of Genomics and Data Science, Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK;
Robert Gerszten
Beth Israel Deaconess Medical Center, Boston, MA;
Steven A. Lubitz
Massachusetts General Hospital, Boston, MA;
Kathryn L. Lunetta
Department of Biostatistics, Boston University School of Public Health, Boston, MA;
Angel C.Y. Mak
Department of Medicine, University of California, San Francisco, CA;
Ani Manichaikul
Center for Public Health Genomics, University of Virginia, Charlottesville, VA;Department of Public Health Sciences, University of Virginia, Charlottesville, VA;
Alisa K. Manning
Department of Medicine/Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA;Department of Medicine, Metabolism Program, Massachusetts General Hospital, Boston, MA;Metabolism Program, The Broad Institute of MIT and Harvard, Cambridge, MA;
Rasika A. Mathias
Department of Medicine, Johns Hopkins University, Baltimore, MD;
David D. McManus
Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, MA, USA;
Stephen T. McGarvey
International Health Institute, Brown University, Providence, RI;Department of Epidemiology, Brown University, Providence, RI;Department of Anthropology, Brown University, Providence, RI;
James B. Meigs
Division Of General Internal Medicine, Massachusetts General Hospital, Harvard Medical School, The Broad Institute of MIT and Harvard, Boston, MA;
Deborah A. Meyers
University of Arizona;
Julie L. Mikulla
National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;
Mollie A. Minear
National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;
Braxton Mitchell
Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD;Department of Medicine, University of Maryland School of Medicine, Baltimore, MD;Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, MD;
Sanghamitra Mohanty
Texas Cardiac Arrhythmia Institute, St. David’s Medical Center, Austin, TX, USA;Department of Internal Medicine, Dell Medical School, Austin, TX, USA;
May E. Montasser
Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD;Department of Medicine, University of Maryland School of Medicine, Baltimore, MD;
Courtney Montgomery
Division of Genomics and Data Science, Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK;
Alanna C. Morrison
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;
Joanne M. Murabito
Department of Medicine, Boston University School of Medicine, Boston, MA;
Andrea Natale
Texas Cardiac Arrhythmia Institute, St. David’s Medical Center, Austin, TX, USA;Department of Internal Medicine, Dell Medical School, Austin, TX, USA;
Pradeep Natarajan
Department of Medicine, Harvard Medical School, Boston, MA;Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA;Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA;Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA;
Sarah C. Nelson
Department of Biostatistics, University of Washington, Seattle, WA;
Kari E. North
Department of Epidemiology, University of North Carolina, Chapel Hill, NC;
Jeffrey R. O’Connell
Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD;Department of Medicine, University of Maryland School of Medicine, Baltimore, MD;
Nicholette D. Palmer
Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC;
Nathan Pankratz
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN;
Gina M. Peloso
Department of Biostatistics, Boston University School of Public Health, Boston, MA;
Patricia A. Peyser
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI;
Wendy S. Post
Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD;
Bruce M. Psaty
Department of Medicine, University of Washington, Seattle, WA;Cardiovascular Health Research Unit, University of Washington, Seattle, WA;Department of Epidemiology, University of Washington, Seattle, WA;Department of Health Services, University of Washington, Seattle, WA;Kaiser Permanente Washington Health Research Institute, Seattle, WA;
D.C. Rao
Division of Biostatistics, Washington University in St. Louis, St. Louis, MO;
Susan Redline
Department of Medicine, Harvard Medical School, Boston, MA;Department of Medicine, Brigham and Women’s Hospital, Boston, MA;
Alexander P. Reiner
Department of Epidemiology, University of Washington, Seattle, WA;Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA;
Dan Roden
Vanderbilt University, Nashville, TN;
Jerome I. Rotter
Department of Pediatrics, The Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA;Department of Medicine, The Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA;
Ingo Ruczinski
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD;
Chloé Sarnowski
Department of Biostatistics, Boston University School of Public Health, Boston, MA;
Sebastian Schoenherr
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria;
Jeong-Sun Seo
Precision Medicine Center, Seoul National University Bundang Hospital, Seongnam, Republic of Korea;Macrogen Inc., Seoul, Republic of Korea;Gong Wu Genomic Medicine Institute, Seoul National University Bundang Hospital, Seongnam, Republic of Korea;
Sudha Seshadri
Framingham Heart Study, Framingham, MA;Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, University of Texas Health Sciences Center at San Antonio, San Antonio, TX;
Vivien A. Sheehan
Department of Pediatrics, Division of Hematology/Oncology, Baylor College of Medicine, Houston, TX;
M. Benjamin Shoemaker
Vanderbilt University, Nashville, TN;
Albert V. Smith
Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI;
Nicholas L. Smith
Cardiovascular Health Research Unit, University of Washington, Seattle, WA;Department of Epidemiology, University of Washington, Seattle, WA;Kaiser Permanente Washington Health Research Institute, Seattle, WA;Seattle Epidemiologic Research and Information Center, Veterans Administration Puget Sound Health Care System, Seattle, WA;
Jennifer A. Smith
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI;Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI;
Nona Sotoodehnia
Cardiovascular Health Research Unit, University of Washington, Seattle, WA;
Adrienne M. Stilp
Department of Biostatistics, University of Washington, Seattle, WA;
Weihong Tang
Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA;
Kent D. Taylor
Department of Pediatrics, The Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA;
Marilyn Telen
Duke University;
Timothy A. Thornton
Department of Biostatistics, University of Washington, Seattle, WA;
Russell P. Tracy
University of Vermont, Burlington, VT;
David J. Van Den Berg
University of Southern California, Center for Genetic Epidemiology, Department of Preventive Medicine, Los Angeles, CA;
Ramachandran S. Vasan
Department of Medicine, Boston University School of Medicine, Boston, MA;Framingham Heart Study, Framingham, MA;
Karine A. Viaud-Martinez
Illumina Clinical Genomics Laboratory Services, San Diego, CA;
Scott Vrieze
Department of Psychology, University of Minnesota, Minneapolis, MN;
Daniel E Weeks
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA;Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA;
Bruce S. Weir
Department of Biostatistics, University of Washington, Seattle, WA;
Scott T. Weiss
Department of Medicine, Harvard Medical School, Boston, MA;Department of Medicine, Brigham and Women’s Hospital, Boston, MA;Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA;Brigham and Women’s Hospital, Boston, MA;
Lu-Chen Weng
Massachusetts General Hospital, Boston, MA;
Cristen J. Willer
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI;Department of Internal Medicine, University of Michigan, Ann Arbor, MI;Department of Human Genetics, University of Michigan, Ann Arbor, MI;
Yingze Zhang
Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA;Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA;Department of Medicine, University of Pittsburgh, Pittsburgh, PA;
Xutong Zhao
Department of Biostatistics, University of Michigan, Ann Arbor, MI;
Donna K. Arnett
Department of Epidemiology, University of Kentucky, Lexington, KY;
Allison E. Ashley-Koch
Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC;
Kathleen C. Barnes
School of Medicine, University of Colorado, Aurora, CO;
Eric Boerwinkle
University of Texas Health Science Center at Houston, Houston, TX;Baylor College of Medicine Human Genome Sequencing Center, Houston, TX;
Stacey Gabriel
The Broad Institute of MIT and Harvard, Cambridge, MA;
Richard Gibbs
Baylor College of Medicine Human Genome Sequencing Center, Houston, TX;
Kenneth M. Rice
Department of Biostatistics, University of Washington, Seattle, WA;
Stephen S. Rich
Center for Public Health Genomics, University of Virginia, Charlottesville, VA;Department of Public Health Sciences, University of Virginia, Charlottesville, VA;
Edwin Silverman
Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA;
Pankaj Qasba
National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;
Weiniu Gan
National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;
George J. Papanicolaou
National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;
Deborah A. Nickerson
Department of Genome Sciences, University of Washington, Seattle, WA;Northwest Genomics Center, Seattle, WA;Brotman Baty Institute, Seattle, WA;
Sharon R. Browning
Department of Biostatistics, University of Washington, Seattle, WA;
Michael C. Zody
New York Genome Center, New York, NY;
Sebastian Zöllner
Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI;Department of Psychiatry, University of Michigan, Ann Arbor, MI;
James G. Wilson
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS;
L Adrienne Cupples
Department of Biostatistics, Boston University School of Public Health, Boston, MA;Framingham Heart Study, Framingham, MA;
Cathy C. Laurie
Department of Biostatistics, University of Washington, Seattle, WA;
Cashell E. Jaquish
National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;
Ryan D. Hernandez
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA;Department of Human Genetics, McGill University, Montreal, Canada
Timothy D. O’Connor
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD;Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD;Department of Medicine, University of Maryland School of Medicine, Baltimore, MD;
Gonçalo R. Abecasis
Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI;
Summary paragraph
The Trans-Omics for Precision Medicine (TOPMed) program seeks to elucidate the genetic architecture and disease biology of heart, lung, blood, and sleep disorders, with the ultimate goal of improving diagnosis, treatment, and prevention. The initial phases of the program focus on whole genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here, we describe TOPMed goals and design as well as resources and early insights from the sequence data. The resources include a variant browser, a genotype imputation panel, and sharing of genomic and phenotypic data via dbGaP. In 53,581 TOPMed samples, >400 million single-nucleotide and insertion/deletion variants were detected by alignment with the reference genome. Additional novel variants are detectable through assembly of unmapped reads and customized analysis in highly variable loci. Among the >400 million variants detected, 97% have frequency <1% and 46% are singletons. These rare variants provide insights into mutational processes and recent human evolutionary history. The nearly complete catalog of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and non-coding sequence variants to phenotypic variation. Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and extends the reach of nearly all genome-wide association studies to include variants down to ~0.01% in frequency.
Copyright
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 4.0 International license.
Posted March 06, 2019.
Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program
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, Quenna Wong, François Aguet, Christine Albert, Alvaro Alonso, Kristin G. Ardlie, Stella Aslibekyan, Paul L. Auer, John Barnard, R. Graham Barr, 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, 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, Diane Fatkin, 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, 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 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, 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, Jeong-Sun Seo, Sudha Seshadri, Vivien A. Sheehan, M. Benjamin Shoemaker, Albert V. Smith, 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 Silverman, Pankaj Qasba, Weiniu Gan, Trans-Omics for Precision Medicine (TOPMed) Program, TOPMed Population Genetics Working Group, 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
bioRxiv 563866; doi: https://doi.org/10.1101/563866
Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program
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, Quenna Wong, François Aguet, Christine Albert, Alvaro Alonso, Kristin G. Ardlie, Stella Aslibekyan, Paul L. Auer, John Barnard, R. Graham Barr, 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, 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, Diane Fatkin, 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, 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 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, 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, Jeong-Sun Seo, Sudha Seshadri, Vivien A. Sheehan, M. Benjamin Shoemaker, Albert V. Smith, 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 Silverman, Pankaj Qasba, Weiniu Gan, Trans-Omics for Precision Medicine (TOPMed) Program, TOPMed Population Genetics Working Group, 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
bioRxiv 563866; doi: https://doi.org/10.1101/563866
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