Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program
Daniel Taliun(University of Michigan), Daniel Harris(University of Maryland, Baltimore), Michael D. Kessler(University of Maryland, Baltimore), Jedidiah Carlson(University of Washington), Zachary A. Szpiech(Pennsylvania State University), Raúl Torres(University of California, San Francisco), Sarah A. Gagliano Taliun(University of Michigan), André Corvelo(New York Genome Center), Stephanie M. Gogarten(University of Washington), Hyun Min Kang(University of Michigan), Achilleas Pitsillides(Boston University), Jonathon LeFaive(University of Michigan), Seung‐been Lee(University of Washington), Xiaowen Tian(University of Washington), Brian L. Browning(University of Washington Medical Center), Sayantan Das(University of Michigan), Anne‐Katrin Emde(New York Genome Center), Wayne E. Clarke(New York Genome Center), Douglas P. Loesch(University of Maryland, Baltimore), Amol C. Shetty(University of Maryland, Baltimore), Thomas W. Blackwell(University of Michigan), Albert V. Smith(University of Michigan), Quenna Wong(University of Washington), Xiaoming Liu(University of South Florida), Matthew P. Conomos(University of Washington), Dean Bobo(Icahn School of Medicine at Mount Sinai), François Aguet(Broad Institute), Christine M. Albert(Massachusetts General Hospital), Álvaro Alonso(Emory University), Kristin Ardlie(Broad Institute), Dan E. Arking(Johns Hopkins University), Stella Aslibekyan(University of Alabama at Birmingham), Paul L. Auer(University of Wisconsin–Milwaukee), John Barnard(Cleveland Clinic), R. Graham Barr(Columbia University Irving Medical Center), Lucas Barwick(Emmes (United States)), Lewis C. Becker(Johns Hopkins University), Rebecca Beer(National Institutes of Health), Emelia J. Benjamin(Boston University), Lawrence F. Bielak(University of Michigan), John Blangero(The University of Texas Rio Grande Valley), Michael Boehnke(University of Michigan), Donald W. Bowden(Wake Forest University), Jennifer A. Brody(University of Washington), Esteban G. Burchard(University of California, San Francisco), Brian E. Cade(Brigham and Women's Hospital), James F. Casella(Johns Hopkins University), Brandon Chalazan(University of British Columbia), Daniel I. Chasman(Brigham and Women's Hospital), Yii‐Der Ida Chen(UCLA Medical Center), Michael H. Cho(Brigham and Women's Hospital), Seung Hoan Choi(Broad Institute), Mina K. Chung(Cleveland Clinic), Clary B. Clish(Broad Institute), Adolfo Correa(Jackson Memorial Hospital), Joanne E. Curran(The University of Texas Rio Grande Valley), Brian Custer(University of California, San Francisco), Dawood Darbar(University of Illinois Chicago), Michelle Daya(University of Colorado Anschutz Medical Campus), Mariza de Andrade(Mayo Clinic in Arizona), Dawn L. DeMeo(Brigham and Women's Hospital), Susan K. Dutcher(James S. McDonnell Foundation), Patrick T. Ellinor(Broad Institute), Leslie S. Emery(University of Washington), Celeste Eng(University of California, San Francisco), Diane Fatkin(Victor Chang Cardiac Research Institute), Tasha E. Fingerlin(National Jewish Health), Lukas Forer(Innsbruck Medical University), Myriam Fornage(The University of Texas Health Science Center at Houston), Nora Franceschini(University of North Carolina at Chapel Hill), Christian Fuchsberger(Eurac Research), Stephanie M. Fullerton(University of Washington), Søren Germer(New York Genome Center), Mark T. Gladwin(University of Pittsburgh), Daniel J. Gottlieb(Brigham and Women's Hospital), Xiuqing Guo(UCLA Medical Center), Michael E. Hall(Jackson Memorial Hospital), Jiang He(Tulane University), Nancy L. Heard‐Costa(Boston University), Susan R. Heckbert(University of Washington), Marguerite R. Irvin(University of Alabama at Birmingham), Jill M. Johnsen(University of Washington), Andrew D. Johnson(National Institutes of Health), Robert C. Kaplan(Albert Einstein College of Medicine), Sharon L. R. Kardia(University of Michigan), Tanika N. Kelly(Tulane University), Shannon Kelly(Pacific Research Institute), Eimear E. Kenny(Icahn School of Medicine at Mount Sinai), Douglas P. Kiel(Broad Institute), Robert Klemmer(University of Michigan), Barbara A. Konkle(University of Washington), Charles Kooperberg(Fred Hutch Cancer Center), Anna Köttgen(Johns Hopkins University), Leslie A. Lange(University of Colorado Denver), Jessica Lasky‐Su(Brigham and Women's Hospital), Daniel Levy(Boston University), Xihong Lin(Harvard University), Keng‐Han Lin(University of Michigan), Chunyu Liu(Boston University), Ruth J. F. Loos(Child Health and Development Institute), Lori Garman(Oklahoma Medical Research Foundation), Robert E. Gerszten(Beth Israel Deaconess Medical Center), Steven A. Lubitz(Massachusetts General Hospital), Kathryn L. Lunetta(Boston University), Angel C. Y. Mak(University of California, San Francisco), Ani Manichaikul(University of Virginia), Alisa K. Manning(Broad Institute), Rasika A. Mathias(Johns Hopkins University), David D. McManus(University of Massachusetts Chan Medical School), Stephen T. McGarvey(Brown University), James B. Meigs(Broad Institute), Deborah A. Meyers(University of Arizona), Julie Mikulla(National Institutes of Health), Mollie Minear(National Institutes of Health), Braxton D. Mitchell(University of Maryland, Baltimore), Sanghamitra Mohanty(Dell Children's Medical Center of Central Texas), May E. Montasser(University of Maryland, Baltimore), Courtney G. Montgomery(Oklahoma Medical Research Foundation), Alanna C. Morrison(The University of Texas Health Science Center at Houston), Joanne M. Murabito(Boston University), Andrea Natale(St David's Medical Center), Pradeep Natarajan(Broad Institute), Sarah C. Nelson(University of Washington), Kari E. North(University of North Carolina at Chapel Hill), Jeffrey R. O’Connell(University of Maryland, Baltimore), Nicholette D. Palmer(Wake Forest University), Nathan Pankratz(University of Minnesota), Gina M. Peloso(Boston University), Patricia A. Peyser(University of Michigan), Jacob Pleiness(University of Michigan), Wendy S. Post(Johns Hopkins University), Bruce M. Psaty(Kaiser Permanente Washington Health Research Institute), D. C. Rao(Washington University in St. Louis), Susan Redline(Brigham and Women's Hospital), Alex P. Reiner(University of Washington), Dan M. Roden(Vanderbilt University Medical Center), Jerome I. Rotter(UCLA Medical Center), Ingo Ruczinski(Johns Hopkins University), Chloé Sarnowski(Boston University), Sebastian Schoenherr(Innsbruck Medical University), David A. Schwartz(University of Colorado Denver), Jeong‐Sun Seo(Seoul National University Bundang Hospital), Sudha Seshadri(The University of Texas at San Antonio Health Science Center), Vivien Sheehan(Emory University), Wayne H.-H. Sheu(Taichung Veterans General Hospital), M. Benjamin Shoemaker(Vanderbilt University Medical Center), Nicholas L. Smith(Kaiser Permanente Washington Health Research Institute), Jennifer A. Smith(University of Michigan), Nona Sotoodehnia(University of Washington), Adrienne M. Stilp(University of Washington), Weihong Tang(University of Minnesota), Kent D. Taylor(UCLA Medical Center), Marilyn J. Telen(Duke University), Timothy A. Thornton(University of Washington), Russell P. Tracy(University of Vermont), David Van Den Berg(University of Southern California), Ramachandran S. Vasan(Boston University), Karine A. Viaud‐Martinez(Illumina (United States)), Scott Vrieze(University of Minnesota), Daniel E. Weeks(University of Pittsburgh), Bruce S. Weir(University of Washington), Scott T. Weiss(Brigham and Women's Hospital), Lu‐Chen Weng(Massachusetts General Hospital), Cristen J. Willer(University of Michigan), Yingze Zhang(University of Pittsburgh), Xutong Zhao(University of Michigan), Donna K. Arnett(University of Kentucky), Allison E. Ashley‐Koch(Duke Medical Center), Kathleen C. Barnes(University of Colorado Anschutz Medical Campus), Eric Boerwinkle(Baylor College of Medicine), Stacey Gabriel(Broad Institute), Richard A. Gibbs(Baylor College of Medicine), Kenneth Rice(University of Washington), Stephen S. Rich(University of Virginia), Edwin K. Silverman(Brigham and Women's Hospital), Pankaj Qasba(National Institutes of Health), Weiniu Gan(National Institutes of Health), Namiko Abe(New York Genome Center), Laura Almasy(Children's Hospital of Philadelphia), Seth A. Ament(University of Maryland, Baltimore), Peter Anderson(University of Washington), Pramod Anugu(University of Mississippi), Deborah Applebaum‐Bowden(National Institutes of Health), Tim Assimes(Stanford University), Dimitrios Avramopoulos(Johns Hopkins University), Emily Barron‐Casella(Johns Hopkins University), Terri Beaty(Johns Hopkins University), Gerald J. Beck(Cleveland Clinic), Diane M. Becker(Johns Hopkins University), Amber L. Beitelshees(University of Maryland, Baltimore), Takis Benos(University of Pittsburgh), Marcos Bezerra(Fundação Hemopa), Joshua C. Bis(University of Washington), Russell Bowler(National Jewish Health), Ulrich Broeckel(Medical College of Wisconsin), Jai Broome(University of Washington), Karen Bunting(New York Genome Center), Carlos D. Bustamante(Stanford University), Erin Buth(University of Washington), Jonathan Cardwell(University of Colorado Denver), Vincent J. Carey(Brigham and Women's Hospital), Cara L. Carty(Washington State University), Richard Casaburi(University of California, Los Angeles), Peter J. Castaldi(Brigham and Women's Hospital), Mark Chaffin(Broad Institute), Christy Chang(University of Maryland, Baltimore), Yi‐Cheng Chang(National Taiwan University), Sameer Chavan(University of Colorado Denver), Bo‐Juen Chen(New York Genome Center), Wei‐Min Chen(University of Virginia), Lee‐Ming Chuang(National Taiwan University), Ren‐Hua Chung(National Health Research Institutes), Suzy Comhair(Cleveland Clinic), Elaine Cornell(University of Vermont), Carolyn Crandall(University of California, Los Angeles), James D. Crapo(National Jewish Health), Jeffrey L. Curtis(University of Michigan), Coleen Damcott(University of Maryland, Baltimore), Sean P. David(University of Illinois Chicago), Colleen Davis(University of Washington), Lisa de las Fuentes(Washington University in St. Louis), Michael R. DeBaun(Vanderbilt University), Ranjan Deka(University of Cincinnati), Scott E. Devine(University of Maryland, Baltimore), Qing Duan(University of North Carolina at Chapel Hill), Ravi Duggirala(The University of Texas Rio Grande Valley), Jon Peter Durda(University of Vermont), Charles B. Eaton(Brown University), Lynette Ekunwe(University of Mississippi), Adel Boueiz(Harvard University), Serpil C. Erzurum(Cleveland Clinic), Charles R. Farber(University of Virginia), Matthew Flickinger(University of Michigan), Myriam Fornage(The University of Texas Health Science Center at Houston), Chris Frazar(University of Washington), Mao Fu(University of Maryland, Baltimore), Lucinda Fulton(Washington University in St. Louis), Shanshan Gao(University of Colorado Denver), Yan Gao(University of Mississippi), Margery Gass(Fred Hutch Cancer Center), Bruce D. Gelb(Icahn School of Medicine at Mount Sinai), Xiaoqi Geng(University of Michigan), Mark W. Geraci(Indiana University – Purdue University Indianapolis), Auyon Ghosh(Brigham and Women's Hospital), Chris Gignoux(Stanford University), David C. Glahn(Yale University), Da‐Wei Gong(University of Maryland, Baltimore), Harald H.H. Göring(The University of Texas Rio Grande Valley), Sharon Graw(University of Colorado Anschutz Medical Campus), Daniel Grine(University of Colorado Denver), C. Charles Gu(Washington University in St. Louis), Yue Guan(University of Maryland, Baltimore), Namrata Gupta(Broad Institute), Jeff Haessler(Fred Hutch Cancer Center), Nicola L. Hawley(Yale University), Ben Heavner(University of Washington), David Herrington(Atrium Health Wake Forest Baptist), Craig P. Hersh(Brigham and Women's Hospital), Bertha Hidalgo(University of Alabama at Birmingham), James E. Hixson(The University of Texas Health Science Center at Houston), Brian D. Hobbs(Brigham and Women's Hospital), John E. Hokanson(University of Colorado Denver), Elliott Hong(University of Maryland, Baltimore), Karin F. Hoth(University of Iowa), Chao A. Hsiung(National Health Research Institutes), Yi‐Jen Hung(Tri-Service General Hospital), Haley Huston(Bloodworks Northwest), Chii Min Hwu(Taichung Veterans General Hospital), Rebecca Jackson(The Ohio State University Wexner Medical Center), Deepti Jain(University of Washington), Min A. Jhun(University of Michigan), Craig Johnson(University of Washington), Rich Johnston(Emory University), Kimberly Marie Jones(Johns Hopkins University), Sekar Kathiresan(Broad Institute), Alyna Khan(University of Washington), Wonji Kim(Harvard University), Gregory L. Kinney(University of Colorado Denver), Holly Kramer(Loyola University Chicago), Christoph Lange(Harvard University), Ethan M. Lange(University of Colorado Denver), Leslie Lange(University of Colorado Denver), Cecelia Laurie(University of Washington), Meryl S. LeBoff(Brigham and Women's Hospital), Jiwon Lee(Brigham and Women's Hospital), Seunggeun Shawn Lee(University of Washington), Wen‐Jane Lee(Taichung Veterans General Hospital), David Levine(University of Washington), Joshua P. Lewis(University of Maryland, Baltimore), Xiaohui Li, Yun Li(University of North Carolina at Chapel Hill), Henry J. Lin, Honghuang Lin, Keng Han Lin(University of Michigan), Simin Liu(Brown University), Ching‐Ti Liu(Duke University), Yu Liu(Palo Alto University), James Luo(National Institutes of Health), Michael C. Mahaney(The University of Texas Rio Grande Valley), Barry J. Make(Johns Hopkins University), JoAnn Manson(Brigham and Women's Hospital), Lauren Margolin(Broad Institute), Lisa W. Martin(George Washington University), Susan Mathai(University of Colorado Denver), Susanne May(University of Washington), Patrick McArdle(University of Maryland, Baltimore), Merry‐Lynn McDonald(University of Alabama at Birmingham), Sean McFarland(Harvard University Press), Daniel McGoldrick(University of Washington), Caitlin McHugh(University of Washington), Hao Mei(University of Mississippi), Luisa Mestroni(University of Colorado Anschutz Medical Campus), Yuan‐I Min(University of Mississippi), Ryan L. Minster(University of Pittsburgh), Matt Moll(Brigham and Women's Hospital), Arden Moscati(Icahn School of Medicine at Mount Sinai), Solomon K. Musani(University of Mississippi), Stanford Mwasongwe(University of Mississippi), Josyf C. Mychaleckyj(University of Virginia), Girish N. Nadkarni(Icahn School of Medicine at Mount Sinai), Rakhi P. Naik(Johns Hopkins University), Take Naseri(National University of Samoa), Sergeï Nekhai(Howard University), Bonnie Neltner(University of Colorado Denver), Heather M. Ochs‐Balcom(University at Buffalo, State University of New York), David T. Paik(Stanford University), James S. Pankow(University of Minnesota), Afshin Parsa(University of Maryland, Baltimore), Juan M. Peralta(The University of Texas Rio Grande Valley), Marco Perez(Stanford University), James A. Perry(University of Maryland, Baltimore), Ulrike Peters(Fred Hutch Cancer Center), Lawrence S. Phillips(Emory University), Toni I. Pollin(University of Maryland, Baltimore), Julia Powers Becker(University of Colorado Denver), Meher Preethi Boorgula(University of Colorado Denver), Michael Preuß(Icahn School of Medicine at Mount Sinai), Dandi Qiao(Brigham and Women's Hospital), Zhaohui Qin(Emory University), Nicholas Rafaels(University of Colorado Denver), Laura M. Raffield(University of North Carolina at Chapel Hill), Laura J. Rasmussen‐Torvik(Northwestern University), Aakrosh Ratan(University of Virginia), Robert M. Reed(University of Maryland, Baltimore), Elizabeth A. Regan(National Jewish Health), Muagututi‘a Sefuiva Reupena(National University of Samoa), Carolina Roselli(Broad Institute), Pamela Russell(University of Colorado Denver), Sarah Ruuska(Bloodworks Northwest), Kathleen A. Ryan(University of Maryland, Baltimore), Éster Cerdeira Sabino(Universidade de São Paulo), Danish Saleheen(Columbia University), Shabnam Salimi(University of Maryland, Baltimore), Steven L. Salzberg(Johns Hopkins University), Kevin Sandow, Vijay G. Sankaran(Broad Institute), Christopher Scheller(University of Michigan), Ellen M. Schmidt(University of Michigan), Karen Schwander(Washington University in St. Louis), Frank C. Sciurba(University of Pittsburgh), Christine E. Seidman(Harvard University), Jonathan G. Seidman(Harvard University), Stephanie L. Sherman(Emory University), Aniket Shetty(University of Maryland, Baltimore), Wayne Hui-Heng Sheu(Taichung Veterans General Hospital), B. Silver(UMass Memorial Health Care), J. G. Smith(University of Washington), Tanja Smith(New York Genome Center), Sylvia Smoller(Albert Einstein College of Medicine), Beverly Snively(Atrium Health Wake Forest Baptist), M Snyder(Stanford University), Tamar Sofer(Brigham and Women's Hospital), Garrett Storm(University of Colorado Denver), Elizabeth A. Streeten(University of Maryland, Baltimore), Yun Ju Sung(Washington University in St. Louis), Jody Sylvia(Brigham and Women's Hospital), Adam A. Szpiro(University of Washington), Carole Sztalryd(University of Maryland, Baltimore), Hua Tang(Stanford University), Margaret A. Taub(Johns Hopkins University), Matthew R.G. Taylor(University of Colorado Denver), Simeon I. Taylor(University of Maryland, Baltimore), Machiko Threlkeld(University of Washington), Lesley Tinker(Fred Hutch Cancer Center), David Tirschwell(University of Washington), Sarah A. Tishkoff(University of Pennsylvania), Hemant K. Tiwari(University of Alabama at Birmingham), Catherine Tong(University of Washington), Michael Y. Tsai(University of Minnesota), Dhananjay Vaidya(Johns Hopkins University), Peter VandeHaar(University of Michigan), Tarik Walker(University of Colorado Denver), Robert L. Wallace(University of Iowa), Avram Walts(University of Colorado Denver), Fei Fei Wang(University of Washington), Heming Wang(Brigham and Women's Hospital), Karol Watson(University of California, Los Angeles), Jennifer Wessel(Indiana University – Purdue University Indianapolis), Kayleen Williams(University of Washington), L. Keoki Williams(Henry Ford Health System), Carla G. Wilson(Brigham and Women's Hospital), Joseph C. Wu(Stanford University), Huichun Xu(University of Maryland, Baltimore), Lisa R. Yanek(Johns Hopkins University), Ivana V. Yang(University of Colorado Denver), Rongze Yang(University of Maryland, Baltimore), Norann A. Zaghloul(University of Maryland, Baltimore), Maryam Zekavat(Broad Institute), Snow Xueyan Zhao(National Jewish Health), Wei Zhao(University of Michigan), Degui Zhi(The University of Texas Health Science Center at Houston), Xiang Zhou(University of Michigan), Xiaofeng Zhu(Case Western Reserve University), George Papanicolaou(National Institutes of Health), Deborah A. Nickerson(University of Washington), Sharon R. Browning(University of Washington), Michael C. Zody(New York Genome Center), Sebastian Zöllner(University of Michigan), James G. Wilson(Jackson Memorial Hospital), L. Adrienne Cupples(Boston University), Cathy C. Laurie(University of Washington), Cashell E. Jaquish(National Institutes of Health), Ryan D. Hernandez(QB3), Timothy D. O’Connor(University of Maryland, Baltimore), Gonçalo R. Abecasis(University of Michigan)
Cited by 2,268Open Access
Abstract
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%.
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