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

Author

Listed:
  • Daniel Taliun

    (University of Michigan School of Public Health
    University of Michigan School of Public Health)

  • Daniel N. Harris

    (University of Maryland School of Medicine
    University of Maryland School of Medicine
    University of Maryland School of Medicine)

  • Michael D. Kessler

    (University of Maryland School of Medicine
    University of Maryland School of Medicine
    University of Maryland School of Medicine)

  • Jedidiah Carlson

    (University of Michigan
    University of Washington)

  • Zachary A. Szpiech

    (Pennsylvania State University
    Pennsylvania State University)

  • Raul Torres

    (University of California, San Francisco)

  • Sarah A. Gagliano Taliun

    (University of Michigan School of Public Health
    University of Michigan School of Public Health)

  • André Corvelo

    (New York Genome Center)

  • Stephanie M. Gogarten

    (University of Washington)

  • Hyun Min Kang

    (University of Michigan School of Public Health
    University of Michigan School of Public Health)

  • Achilleas N. Pitsillides

    (Boston University School of Public Health)

  • Jonathon LeFaive

    (University of Michigan School of Public Health
    University of Michigan School of Public Health)

  • Seung-been Lee

    (University of Washington)

  • Xiaowen Tian

    (University of Washington)

  • Brian L. Browning

    (University of Washington)

  • Sayantan Das

    (University of Michigan School of Public Health
    University of Michigan School of Public Health)

  • Anne-Katrin Emde

    (New York Genome Center)

  • Wayne E. Clarke

    (New York Genome Center)

  • Douglas P. Loesch

    (University of Maryland School of Medicine
    University of Maryland School of Medicine
    University of Maryland School of Medicine)

  • Amol C. Shetty

    (University of Maryland School of Medicine
    University of Maryland School of Medicine
    University of Maryland School of Medicine)

  • Thomas W. Blackwell

    (University of Michigan School of Public Health
    University of Michigan School of Public Health)

  • Albert V. Smith

    (University of Michigan School of Public Health
    University of Michigan School of Public Health)

  • Quenna Wong

    (University of Washington)

  • Xiaoming Liu

    (University of South Florida)

  • Matthew P. Conomos

    (University of Washington)

  • Dean M. Bobo

    (Icahn School of Medicine at Mount Sinai)

  • François Aguet

    (The Broad Institute of MIT and Harvard)

  • Christine Albert

    (Massachusetts General Hospital)

  • Alvaro Alonso

    (Emory University)

  • Kristin G. Ardlie

    (The Broad Institute of MIT and Harvard)

  • Dan E. Arking

    (Johns Hopkins University School of Medicine)

  • Stella Aslibekyan

    (University of Alabama)

  • Paul L. Auer

    (University of Wisconsin Milwaukee)

  • John Barnard

    (Cleveland Clinic)

  • R. Graham Barr

    (Columbia University Medical Center
    Columbia University Medical Center)

  • Lucas Barwick

    (The Emmes Corporation)

  • Lewis C. Becker

    (Johns Hopkins University)

  • Rebecca L. Beer

    (National Institutes of Health)

  • Emelia J. Benjamin

    (Boston University School of Medicine
    Boston University School of Public Health
    Framingham Heart Study)

  • Lawrence F. Bielak

    (University of Michigan School of Public Health)

  • John Blangero

    (University of Texas Rio Grande Valley School of Medicine
    University of Texas Rio Grande Valley School of Medicine)

  • Michael Boehnke

    (University of Michigan School of Public Health
    University of Michigan School of Public Health)

  • Donald W. Bowden

    (Wake Forest School of Medicine)

  • Jennifer A. Brody

    (University of Washington
    University of Washington)

  • Esteban G. Burchard

    (University of California, San Francisco
    University of California, San Francisco)

  • Brian E. Cade

    (Harvard Medical School
    Brigham and Women’s Hospital)

  • James F. Casella

    (Johns Hopkins University
    Johns Hopkins University)

  • Brandon Chalazan

    (University of British Columbia)

  • Daniel I. Chasman

    (Brigham and Women’s Hospital
    Harvard Medical School)

  • Yii-Der Ida Chen

    (The Lundquist Institute for Biomedical Innovation, Harbor-UCLA Medical Center)

  • Michael H. Cho

    (Brigham and Women’s Hospital)

  • Seung Hoan Choi

    (The Broad Institute of MIT and Harvard)

  • Mina K. Chung

    (Cleveland Clinic
    Lerner Research Institute, Cleveland Clinic
    Case Western Reserve University)

  • Clary B. Clish

    (The Broad Institute of MIT and Harvard)

  • Adolfo Correa

    (University of Mississippi Medical Center
    University of Mississippi Medical Center
    University of Mississippi Medical Center)

  • Joanne E. Curran

    (University of Texas Rio Grande Valley School of Medicine
    University of Texas Rio Grande Valley School of Medicine)

  • Brian Custer

    (Vitalant Research Institute
    University of California, San Francisco)

  • Dawood Darbar

    (University of Illinois at Chicago)

  • Michelle Daya

    (University of Colorado Anschutz Medical Campus)

  • Mariza Andrade

    (Mayo Clinic)

  • Dawn L. DeMeo

    (Brigham and Women’s Hospital)

  • Susan K. Dutcher

    (Washington University
    Washington University)

  • Patrick T. Ellinor

    (The Broad Institute of MIT and Harvard)

  • Leslie S. Emery

    (University of Washington)

  • Celeste Eng

    (University of California, San Francisco)

  • Diane Fatkin

    (Victor Chang Cardiac Research Institute
    University of New South Wales
    St Vincent’s Hospital)

  • Tasha Fingerlin

    (Center for Genes, Environment and Health)

  • Lukas Forer

    (Medical University of Innsbruck)

  • Myriam Fornage

    (University of Texas Health Science Center at Houston)

  • Nora Franceschini

    (University of North Carolina)

  • Christian Fuchsberger

    (University of Michigan School of Public Health
    University of Michigan School of Public Health
    Medical University of Innsbruck
    Eurac Research)

  • Stephanie M. Fullerton

    (University of Washington School of Medicine)

  • Soren Germer

    (New York Genome Center)

  • Mark T. Gladwin

    (University of Pittsburgh
    University of Pittsburgh
    University of Pittsburgh)

  • Daniel J. Gottlieb

    (VA Boston Healthcare System
    Brigham and Women’s Hospital)

  • Xiuqing Guo

    (The Lundquist Institute for Biomedical Innovation, Harbor-UCLA Medical Center)

  • Michael E. Hall

    (University of Mississippi Medical Center)

  • Jiang He

    (Tulane University
    Tulane University)

  • Nancy L. Heard-Costa

    (Framingham Heart Study
    Boston University School of Medicine)

  • Susan R. Heckbert

    (University of Washington
    University of Washington)

  • Marguerite R. Irvin

    (University of Alabama at Birmingham)

  • Jill M. Johnsen

    (University of Washington
    Bloodworks Northwest Research Institute)

  • Andrew D. Johnson

    (Framingham Heart Study
    Lung, and Blood Institute, National Institutes of Health)

  • Robert Kaplan

    (Albert Einstein College of Medicine)

  • Sharon L. R. Kardia

    (University of Michigan School of Public Health)

  • Tanika Kelly

    (Tulane University)

  • Shannon Kelly

    (Vitalant Research Institute
    UCSF Benioff Children’s Hospital
    UCSF Benioff Children’s Hospital)

  • Eimear E. Kenny

    (Icahn School of Medicine at Mount Sinai)

  • Douglas P. Kiel

    (The Broad Institute of MIT and Harvard
    Harvard Medical School
    Hebrew SeniorLife
    Beth Israel Deaconess Medical Center)

  • Robert Klemmer

    (University of Michigan School of Public Health
    University of Michigan School of Public Health)

  • Barbara A. Konkle

    (University of Washington
    Bloodworks Northwest Research Institute)

  • Charles Kooperberg

    (Fred Hutchinson Cancer Research Center)

  • Anna Köttgen

    (Johns Hopkins University
    University of Freiburg)

  • Leslie A. Lange

    (University of Colorado at Denver)

  • Jessica Lasky-Su

    (Harvard Medical School
    Brigham and Women’s Hospital
    Brigham and Women’s Hospital
    Brigham and Women’s Hospital)

  • Daniel Levy

    (Boston University School of Medicine
    Framingham Heart Study
    Lung, and Blood Institute, National Institutes of Health)

  • Xihong Lin

    (Harvard University)

  • Keng-Han Lin

    (University of Michigan School of Public Health
    University of Michigan School of Public Health)

  • Chunyu Liu

    (Boston University School of Public Health)

  • Ruth J. F. Loos

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Lori Garman

    (Oklahoma Medical Research Foundation)

  • Robert Gerszten

    (Beth Israel Deaconess Medical Center)

  • Steven A. Lubitz

    (Massachusetts General Hospital)

  • Kathryn L. Lunetta

    (Boston University School of Public Health)

  • Angel C. Y. Mak

    (University of California, San Francisco)

  • Ani Manichaikul

    (University of Virginia
    University of Virginia)

  • Alisa K. Manning

    (Harvard Medical School
    Mongan Institute, Massachusetts General Hospital
    The Broad Institute of MIT and Harvard)

  • Rasika A. Mathias

    (Johns Hopkins University)

  • David D. McManus

    (University of Massachusetts Medical School)

  • Stephen T. McGarvey

    (Brown University
    Brown University
    Brown University)

  • James B. Meigs

    (The Broad Institute of MIT and Harvard)

  • Deborah A. Meyers

    (University of Arizona)

  • Julie L. Mikulla

    (National Institutes of Health)

  • Mollie A. Minear

    (National Institutes of Health)

  • Braxton D. Mitchell

    (University of Maryland School of Medicine
    University of Maryland School of Medicine
    Baltimore Veterans Administration Medical Center)

  • Sanghamitra Mohanty

    (St David’s Medical Center
    Dell Medical School)

  • May E. Montasser

    (University of Maryland School of Medicine
    University of Maryland School of Medicine)

  • Courtney Montgomery

    (Oklahoma Medical Research Foundation)

  • Alanna C. Morrison

    (University of Texas Health Science Center at Houston)

  • Joanne M. Murabito

    (Boston University School of Medicine)

  • Andrea Natale

    (St David’s Medical Center)

  • Pradeep Natarajan

    (Harvard Medical School
    The Broad Institute of MIT and Harvard
    Massachusetts General Hospital
    Massachusetts General Hospital)

  • Sarah C. Nelson

    (University of Washington)

  • Kari E. North

    (University of North Carolina)

  • Jeffrey R. O’Connell

    (University of Maryland School of Medicine
    University of Maryland School of Medicine)

  • Nicholette D. Palmer

    (Wake Forest School of Medicine)

  • Nathan Pankratz

    (University of Minnesota)

  • Gina M. Peloso

    (Boston University School of Public Health)

  • Patricia A. Peyser

    (University of Michigan School of Public Health)

  • Jacob Pleiness

    (University of Michigan School of Public Health
    University of Michigan School of Public Health)

  • Wendy S. Post

    (Johns Hopkins University)

  • Bruce M. Psaty

    (University of Washington
    University of Washington
    University of Washington
    University of Washington)

  • D. C. Rao

    (Washington University in St Louis)

  • Susan Redline

    (Harvard Medical School
    Brigham and Women’s Hospital)

  • Alexander P. Reiner

    (University of Washington
    Fred Hutchinson Cancer Research Center)

  • Dan Roden

    (Vanderbilt University Medical Center)

  • Jerome I. Rotter

    (The Lundquist Institute for Biomedical Innovation, Harbor-UCLA Medical Center)

  • Ingo Ruczinski

    (Johns Hopkins Bloomberg School of Public Health)

  • Chloé Sarnowski

    (Boston University School of Public Health)

  • Sebastian Schoenherr

    (Medical University of Innsbruck)

  • David A. Schwartz

    (University of Colorado at Denver)

  • Jeong-Sun Seo

    (Seoul National University Bundang Hospital
    Macrogen Inc
    Seoul National University Bundang Hospital)

  • Sudha Seshadri

    (Framingham Heart Study
    University of Texas Health Sciences Center at San Antonio)

  • Vivien A. Sheehan

    (Emory University School of Medicine
    Children’s Healthcare of Atlanta)

  • Wayne H. Sheu

    (Taichung Veterans General Hospital Taiwan)

  • M. Benjamin Shoemaker

    (Vanderbilt University Medical Center)

  • Nicholas L. Smith

    (University of Washington
    Kaiser Permanente Washington Health Research Institute
    Seattle Epidemiologic Research and Information Center, Department of Veterans Affairs Office of Research and Development)

  • Jennifer A. Smith

    (University of Michigan School of Public Health
    University of Michigan)

  • Nona Sotoodehnia

    (University of Washington)

  • Adrienne M. Stilp

    (University of Washington)

  • Weihong Tang

    (University of Minnesota)

  • Kent D. Taylor

    (The Lundquist Institute for Biomedical Innovation, Harbor-UCLA Medical Center)

  • Marilyn Telen

    (Duke University)

  • Timothy A. Thornton

    (University of Washington)

  • Russell P. Tracy

    (University of Vermont Larner College of Medicine)

  • David J. Berg

    (University of Southern California)

  • Ramachandran S. Vasan

    (Boston University School of Medicine
    Framingham Heart Study)

  • Karine A. Viaud-Martinez

    (Illumina Laboratory Services, Illumina Inc)

  • Scott Vrieze

    (University of Minnesota)

  • Daniel E. Weeks

    (University of Pittsburgh
    University of Pittsburgh)

  • Bruce S. Weir

    (University of Washington)

  • Scott T. Weiss

    (Harvard Medical School
    Brigham and Women’s Hospital
    Brigham and Women’s Hospital
    Brigham and Women’s Hospital)

  • Lu-Chen Weng

    (Massachusetts General Hospital)

  • Cristen J. Willer

    (University of Michigan
    University of Michigan
    University of Michigan)

  • Yingze Zhang

    (University of Pittsburgh
    University of Pittsburgh
    University of Pittsburgh)

  • Xutong Zhao

    (University of Michigan School of Public Health
    University of Michigan School of Public Health)

  • Donna K. Arnett

    (University of Kentucky)

  • Allison E. Ashley-Koch

    (Duke University Medical Center)

  • Kathleen C. Barnes

    (University of Colorado Anschutz Medical Campus)

  • Eric Boerwinkle

    (University of Texas Health Science Center at Houston
    Baylor College of Medicine Human Genome Sequencing Center)

  • Stacey Gabriel

    (The Broad Institute of MIT and Harvard)

  • Richard Gibbs

    (Baylor College of Medicine Human Genome Sequencing Center)

  • Kenneth M. Rice

    (University of Washington)

  • Stephen S. Rich

    (University of Virginia
    University of Virginia)

  • Edwin K. Silverman

    (Brigham and Women’s Hospital)

  • Pankaj Qasba

    (National Institutes of Health)

  • Weiniu Gan

    (National Institutes of Health)

  • George J. Papanicolaou

    (National Institutes of Health)

  • Deborah A. Nickerson

    (University of Washington
    Northwest Genomics Center
    Brotman Baty Institute)

  • Sharon R. Browning

    (University of Washington)

  • Michael C. Zody

    (New York Genome Center)

  • Sebastian Zöllner

    (University of Michigan School of Public Health
    University of Michigan School of Public Health
    University of Michigan)

  • James G. Wilson

    (University of Mississippi Medical Center)

  • L. Adrienne Cupples

    (Boston University School of Public Health
    Framingham Heart Study)

  • Cathy C. Laurie

    (University of Washington)

  • Cashell E. Jaquish

    (National Institutes of Health)

  • Ryan D. Hernandez

    (University of California, San Francisco
    McGill University
    University of California, San Francisco
    University of California, San Francisco)

  • Timothy D. O’Connor

    (University of Maryland School of Medicine
    University of Maryland School of Medicine
    University of Maryland School of Medicine)

  • Gonçalo R. Abecasis

    (University of Michigan School of Public Health)

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%.

Suggested Citation

  • 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 & Achille, 2021. "Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program," Nature, Nature, vol. 590(7845), pages 290-299, February.
    • Handle: RePEc:nat:nature:v:590:y:2021:i:7845:d:10.1038_s41586-021-03205-y
    DOI: 10.1038/s41586-021-03205-y
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    5. Mateus H. Gouveia & Amy R. Bentley & Thiago P. Leal & Eduardo Tarazona-Santos & Carlos D. Bustamante & Adebowale A. Adeyemo & Charles N. Rotimi & Daniel Shriner, 2023. "Unappreciated subcontinental admixture in Europeans and European Americans and implications for genetic epidemiology studies," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
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