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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
1Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI;
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Daniel N. Harris
2Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD;
3Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD;
4Department of Medicine, University of Maryland School of Medicine, Baltimore, MD;
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Michael D. Kessler
2Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD;
3Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD;
4Department of Medicine, University of Maryland School of Medicine, Baltimore, MD;
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Jedidiah Carlson
5Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI;
6Department of Genome Sciences, University of Washington, Seattle, WA;
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Zachary A. Szpiech
7Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA;
8Department of Biological Sciences, Auburn University, Auburn, AL;
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Raul Torres
9Biomedical Sciences Graduate Program, University of California, San Francisco, CA;
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Sarah A. Gagliano Taliun
1Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI;
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André Corvelo
10New York Genome Center, New York, NY;
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Stephanie M. Gogarten
11Department of Biostatistics, University of Washington, Seattle, WA;
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Hyun Min Kang
1Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI;
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Achilleas N. Pitsillides
12Department of Biostatistics, Boston University School of Public Health, Boston, MA;
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Jonathon LeFaive
1Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI;
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Seung-been Lee
6Department of Genome Sciences, University of Washington, Seattle, WA;
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Xiaowen Tian
11Department of Biostatistics, University of Washington, Seattle, WA;
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Brian L. Browning
13Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, WA;
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Sayantan Das
1Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI;
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Anne-Katrin Emde
10New York Genome Center, New York, NY;
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Wayne E. Clarke
10New York Genome Center, New York, NY;
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Douglas P. Loesch
2Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD;
3Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD;
4Department of Medicine, University of Maryland School of Medicine, Baltimore, MD;
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Amol C. Shetty
2Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD;
3Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD;
4Department of Medicine, University of Maryland School of Medicine, Baltimore, MD;
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Thomas W. Blackwell
1Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI;
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Quenna Wong
11Department of Biostatistics, University of Washington, Seattle, WA;
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François Aguet
14The Broad Institute of MIT and Harvard, Cambridge, MA;
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Christine Albert
15Massachusetts General Hospital, Boston, MA;
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Alvaro Alonso
16Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA;
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Kristin G. Ardlie
14The Broad Institute of MIT and Harvard, Cambridge, MA;
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Stella Aslibekyan
17University of Alabama, Birmingham, AL;
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Paul L. Auer
18Zilber School of Public Health, University of Wisconsin Milwaukee, Milwaukee, WI;
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John Barnard
19Cleveland Clinic, Cleveland, OH;
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R. Graham Barr
20Department of Medicine, Columbia University Medical Center, New York, NY;
21Department of Epidemiology, Columbia University Medical Center, New York, NY;
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Lewis C. Becker
22Johns Hopkins University, Baltimore, MD;
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Rebecca L. Beer
23National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;
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Emelia J. Benjamin
24Department of Medicine, Boston University School of Medicine, Boston, MA;
25Department of Epidemiology, Boston University School of Public Health, Boston, MA;
26Framingham Heart Study, Framingham, MA;
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Lawrence F. Bielak
27Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI;
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John Blangero
28Department of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX;
29South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX;
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Michael Boehnke
1Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI;
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Donald W. Bowden
30Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC;
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Jennifer A. Brody
31Department of Medicine, University of Washington, Seattle, WA;
32Cardiovascular Health Research Unit, University of Washington, Seattle, WA;
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Esteban G. Burchard
7Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA;
33Department of Medicine, University of California, San Francisco, CA;
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Brian E. Cade
34Department of Medicine, Harvard Medical School, Boston, MA;
35Department of Medicine, Brigham and Women’s Hospital, Boston, MA;
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James F. Casella
36Department of Pediatrics, Johns Hopkins University, Baltimore, MD;
37Division of Pediatric Hematology, Johns Hopkins University, Baltimore, MD;
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Brandon Chalazan
38Department of Medical Genetics, University of British Columbia, Vancouver, BC;
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Yii-Der Ida Chen
39Department of Pediatrics, The Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA;
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Michael H. Cho
40Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA;
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Seung Hoan Choi
14The Broad Institute of MIT and Harvard, Cambridge, MA;
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Mina K. Chung
41Department of Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, Cleveland, Ohio, USA;
42Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA;
43Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA;
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Clary B. Clish
44Metabolomics Platform, The Broad Institute of MIT and Harvard, Cambridge, MA;
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Adolfo Correa
45Department of Medicine, University of Mississippi Medical Center, Jackson, MS;
46Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS;
47Department of Population Health Science, University of Mississippi Medical Center, Jackson, MS;
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Joanne E. Curran
28Department of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX;
29South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX;
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Brian Custer
48Vitalant Research Institute, San Francisco, CA, USA;
49Department of Laboratory Medicine, UCSF, San Francisco, CA, USA;
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Dawood Darbar
50Department of Medicine, University of Illinois at Chicago, Chicago, IL;
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Michelle Daya
51School of Medicine, University of Colorado, Aurora, CO;
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Mariza de Andrade
52Mayo Clinic, Rochester, MN;
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Dawn L. DeMeo
40Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA;
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Susan K. Dutcher
53McDonnell Genome Institute and Department of Genetics, Washington University, St Louis, MO;
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Patrick T. Ellinor
54Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA;
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Leslie S. Emery
11Department of Biostatistics, University of Washington, Seattle, WA;
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Diane Fatkin
55Molecular Cardiology Division, Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia;
56Faculty of Medicine, University of New South Wales, Kensington, NSW, Australia;
57Cardiology Department, St. Vincent’s Hospital, Darlinghurst, NSW, Australia;
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Lukas Forer
58Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria;
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Myriam Fornage
59Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX;
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Nora Franceschini
60Department of Epidemiology, University of North Carolina, Chapel Hill, NC;
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Christian Fuchsberger
1Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI;
61Institute for Biomedicine, Eurac Research, Bolzano, Italy;
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Stephanie M. Fullerton
62Department of Bioethics & Humanities, University of Washington School of Medicine, Seattle, WA;
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Soren Germer
10New York Genome Center, New York, NY;
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Mark T. Gladwin
63Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA;
64Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA;
65Department of Medicine, University of Pittsburgh, Pittsburgh, PA;
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Daniel J. Gottlieb
66VA Boston Healthcare System, Boston, MA;
67Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, Boston, MA;
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Xiuqing Guo
39Department of Pediatrics, The Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA;
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Michael E. Hall
45Department of Medicine, University of Mississippi Medical Center, Jackson, MS;
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Jiang He
68Department of Epidemiology, Tulane University, New Orleans, LA;
69Tulane University Translational Science Institute, Tulane University, New Orleans, LA;
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Nancy L. Heard-Costa
26Framingham Heart Study, Framingham, MA;
70Department of Neurology, Boston University School of Medicine, Boston, MA;
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Susan R. Heckbert
32Cardiovascular Health Research Unit, University of Washington, Seattle, WA;
71Department of Epidemiology, University of Washington, Seattle, WA;
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Marguerite R. Irvin
72Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL;
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Jill M. Johnsen
31Department of Medicine, University of Washington, Seattle, WA;
73Bloodworks Northwest Research Institute, Seattle, WA;
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Andrew D. Johnson
26Framingham Heart Study, Framingham, MA;
74Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Framingham, MA;
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Sharon L.R. Kardia
27Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI;
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Tanika Kelly
68Department of Epidemiology, Tulane University, New Orleans, LA;
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Shannon Kelly
75Department of Epidemiology, Vitalant Research Institute, San Francisco, CA;
76Department of Pediatrics, UCSF Benioff Children’s Hospital, Oakland, CA;
77Division of Pediatric Hematology, UCSF Benioff Children’s Hospital, Oakland, CA;
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Eimear E. Kenny
78Icahn School of Medicine at Mount Sinai, New York, NY;
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Douglas P. Kiel
34Department of Medicine, Harvard Medical School, Boston, MA;
79Marcus Institute for Aging Research/Harvard Medical School, Hebrew SeniorLife, Boston, MA;
80Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA;
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Robert Klemmer
1Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI;
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Barbara A. Konkle
31Department of Medicine, University of Washington, Seattle, WA;
73Bloodworks Northwest Research Institute, Seattle, WA;
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Charles Kooperberg
81Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA;
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Anna Köttgen
82Department of Epidemiology, Johns Hopkins University, Baltimore, MD;
83Institute of Genetic Epidemiology, Medical Center - University of Freiburg, Freiburg, Germany;
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Leslie A. Lange
84Department of Medicine, University of Colorado at Denver, Aurora, CO;
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Jessica Lasky-Su
34Department of Medicine, Harvard Medical School, Boston, MA;
35Department of Medicine, Brigham and Women’s Hospital, Boston, MA;
40Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA;
85Brigham and Women’s Hospital, Boston, MA;
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Daniel Levy
24Department of Medicine, Boston University School of Medicine, Boston, MA;
74Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Framingham, MA;
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Xihong Lin
86Biostatistics and Statistics, Harvard University, Boston, MA;
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Keng-Han Lin
1Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI;
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Chunyu Liu
12Department of Biostatistics, Boston University School of Public Health, Boston, MA;
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Ruth J.F. Loos
87The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA;
88The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA;
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Lori Garman
89Division of Genomics and Data Science, Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK;
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Robert Gerszten
90Beth Israel Deaconess Medical Center, Boston, MA;
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Steven A. Lubitz
15Massachusetts General Hospital, Boston, MA;
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Kathryn L. Lunetta
12Department of Biostatistics, Boston University School of Public Health, Boston, MA;
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Angel C.Y. Mak
33Department of Medicine, University of California, San Francisco, CA;
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Ani Manichaikul
91Center for Public Health Genomics, University of Virginia, Charlottesville, VA;
92Department of Public Health Sciences, University of Virginia, Charlottesville, VA;
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Alisa K. Manning
93Department of Medicine/Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA;
94Department of Medicine, Metabolism Program, Massachusetts General Hospital, Boston, MA;
95Metabolism Program, The Broad Institute of MIT and Harvard, Cambridge, MA;
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Rasika A. Mathias
96Department of Medicine, Johns Hopkins University, Baltimore, MD;
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David D. McManus
97Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, MA, USA;
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Stephen T. McGarvey
98International Health Institute, Brown University, Providence, RI;
99Department of Epidemiology, Brown University, Providence, RI;
100Department of Anthropology, Brown University, Providence, RI;
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James B. Meigs
101Division Of General Internal Medicine, Massachusetts General Hospital, Harvard Medical School, The Broad Institute of MIT and Harvard, Boston, MA;
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Deborah A. Meyers
102University of Arizona;
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Julie L. Mikulla
23National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;
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Mollie A. Minear
23National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;
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Braxton Mitchell
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110Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD;
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31Department of Medicine, University of Washington, Seattle, WA;
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71Department of Epidemiology, University of Washington, Seattle, WA;
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114Vanderbilt University, Nashville, TN;
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58Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria;
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117Precision Medicine Center, Seoul National University Bundang Hospital, Seongnam, Republic of Korea;
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119Gong Wu Genomic Medicine Institute, Seoul National University Bundang Hospital, Seongnam, Republic of Korea;
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Sudha Seshadri
26Framingham Heart Study, Framingham, MA;
120Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, University of Texas Health Sciences Center at San Antonio, San Antonio, TX;
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Vivien A. Sheehan
121Department of Pediatrics, Division of Hematology/Oncology, Baylor College of Medicine, Houston, TX;
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114Vanderbilt University, Nashville, TN;
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1Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI;
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Nicholas L. Smith
32Cardiovascular Health Research Unit, University of Washington, Seattle, WA;
71Department of Epidemiology, University of Washington, Seattle, WA;
112Kaiser Permanente Washington Health Research Institute, Seattle, WA;
122Seattle Epidemiologic Research and Information Center, Veterans Administration Puget Sound Health Care System, Seattle, WA;
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Jennifer A. Smith
27Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI;
123Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI;
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Nona Sotoodehnia
32Cardiovascular Health Research Unit, University of Washington, Seattle, WA;
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Adrienne M. Stilp
11Department of Biostatistics, University of Washington, Seattle, WA;
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124Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA;
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Kent D. Taylor
39Department of Pediatrics, The Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA;
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125Duke University;
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126University of Vermont, Burlington, VT;
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127University of Southern California, Center for Genetic Epidemiology, Department of Preventive Medicine, Los Angeles, CA;
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128Illumina Clinical Genomics Laboratory Services, San Diego, CA;
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129Department of Psychology, University of Minnesota, Minneapolis, MN;
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130Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA;
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34Department of Medicine, Harvard Medical School, Boston, MA;
35Department of Medicine, Brigham and Women’s Hospital, Boston, MA;
40Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA;
85Brigham and Women’s Hospital, Boston, MA;
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Lu-Chen Weng
15Massachusetts General Hospital, Boston, MA;
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Cristen J. Willer
5Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI;
132Department of Internal Medicine, University of Michigan, Ann Arbor, MI;
133Department of Human Genetics, University of Michigan, Ann Arbor, MI;
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Yingze Zhang
63Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA;
64Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA;
65Department of Medicine, University of Pittsburgh, Pittsburgh, PA;
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Xutong Zhao
134Department of Biostatistics, University of Michigan, Ann Arbor, MI;
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135Department of Epidemiology, University of Kentucky, Lexington, KY;
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136Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC;
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51School of Medicine, University of Colorado, Aurora, CO;
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Eric Boerwinkle
137University of Texas Health Science Center at Houston, Houston, TX;
138Baylor College of Medicine Human Genome Sequencing Center, Houston, TX;
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14The Broad Institute of MIT and Harvard, Cambridge, MA;
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138Baylor College of Medicine Human Genome Sequencing Center, Houston, TX;
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91Center for Public Health Genomics, University of Virginia, Charlottesville, VA;
92Department of Public Health Sciences, University of Virginia, Charlottesville, VA;
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40Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA;
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23National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;
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6Department of Genome Sciences, University of Washington, Seattle, WA;
139Northwest Genomics Center, Seattle, WA;
140Brotman Baty Institute, Seattle, WA;
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11Department of Biostatistics, University of Washington, Seattle, WA;
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10New York Genome Center, New York, NY;
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1Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI;
141Department of Psychiatry, University of Michigan, Ann Arbor, MI;
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142Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS;
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12Department of Biostatistics, Boston University School of Public Health, Boston, MA;
26Framingham Heart Study, Framingham, MA;
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Cathy C. Laurie
11Department of Biostatistics, University of Washington, Seattle, WA;
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Cashell E. Jaquish
23National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;
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Ryan D. Hernandez
7Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA;
143Department of Human Genetics, McGill University, Montreal, Canada
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Timothy D. O’Connor
2Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD;
3Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD;
4Department of Medicine, University of Maryland School of Medicine, Baltimore, MD;
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Gonçalo R. Abecasis
1Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI;
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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.

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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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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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