Journal article
Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program
Nature (London), Vol.590(7845), pp.290-299
02/2021
DOI: 10.1038/s41586-021-03205-y
PMCID: PMC7875770
PMID: 33568819
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)
. 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%.
Details
- Title: Subtitle
- Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program
- Creators
- Daniel Taliun - University of MichiganDaniel N Harris - University of Maryland, BaltimoreMichael D Kessler - University of Maryland, BaltimoreJedidiah Carlson - University of MichiganZachary A Szpiech - Pennsylvania State UniversityRaul Torres - University of California, San FranciscoSarah A. Gagliano Taliun - University of MichiganAndré Corvelo - New York Genome CenterStephanie M Gogarten - University of WashingtonHyun Min Kang - University of MichiganAchilleas N Pitsillides - Boston UniversityJonathon LeFaive - University of MichiganSeung-Been Lee - University of WashingtonXiaowen Tian - University of WashingtonBrian L Browning - University of WashingtonSayantan Das - University of MichiganAnne-Katrin Emde - New York Genome CenterWayne E Clarke - New York Genome CenterDouglas P Loesch - University of Maryland, BaltimoreAmol C Shetty - University of Maryland, BaltimoreThomas W Blackwell - University of MichiganAlbert V Smith - University of MichiganQuenna Wong - University of WashingtonXiaoming Liu - University of South FloridaMatthew P Conomos - University of WashingtonDean M Bobo - Icahn School of Medicine at Mount SinaiFrançois Aguet - Broad InstituteChristine Albert - Harvard UniversityAlvaro Alonso - Emory UniversityKristin G Ardlie - Broad InstituteDan E Arking - Johns Hopkins MedicineStella Aslibekyan - University of Alabama at BirminghamPaul L Auer - University of Wisconsin–MilwaukeeJohn Barnard - Cleveland ClinicR Graham Barr - Columbia University Irving Medical CenterLucas Barwick - Emmes (United States)Lewis C Becker - Johns Hopkins UniversityRebecca L Beer - National Institutes of HealthEmelia J Benjamin - Boston UniversityLawrence F Bielak - University of MichiganJohn Blangero - The University of Texas at AustinMichael Boehnke - University of MichiganDonald W Bowden - Wake Forest UniversityJennifer A Brody - University of WashingtonEsteban G Burchard - University of California, San FranciscoBrian E Cade - Harvard UniversityJames F Casella - Johns Hopkins UniversityBrandon Chalazan - University of British ColumbiaDaniel I Chasman - Harvard UniversityYii-Der Ida Chen - The Lundquist InstituteMichael H Cho - Brigham and Women's HospitalSeung Hoan Choi - Broad InstituteMina K Chung - Cleveland Clinic Lerner College of MedicineClary B Clish - Broad InstituteAdolfo Correa - University of Mississippi Medical CenterJoanne E Curran - The University of Texas at AustinBrian Custer - University of California, San FranciscoDawood Darbar - University of Illinois ChicagoMichelle Daya - University of Colorado Anschutz Medical CampusMariza de Andrade - Mayo ClinicDawn L DeMeo - Brigham and Women's HospitalSusan K Dutcher - Washington University in St. LouisPatrick T Ellinor - Broad InstituteLeslie S Emery - University of WashingtonCeleste Eng - University of California, San FranciscoDiane Fatkin - Victor Chang Cardiac Research InstituteTasha Fingerlin - National Jewish HealthLukas Forer - Innsbruck Medical UniversityMyriam Fornage - The University of Texas Health Science Center at HoustonNora Franceschini - University of North Carolina at Chapel HillChristian Fuchsberger - Eurac ResearchStephanie M Fullerton - University of WashingtonSoren Germer - New York Genome CenterMark T Gladwin - University of PittsburghDaniel J Gottlieb - Brigham and Women's HospitalXiuqing Guo - The Lundquist InstituteMichael E Hall - University of Mississippi Medical CenterJiang He - Tulane UniversityNancy L Heard-Costa - Boston UniversitySusan R Heckbert - University of WashingtonMarguerite R Irvin - University of Alabama at BirminghamJill M Johnsen - University of WashingtonAndrew D Johnson - National Institutes of HealthRobert Kaplan - Albert Einstein College of MedicineSharon L R Kardia - University of MichiganTanika Kelly - Tulane UniversityShannon Kelly - UCSF Benioff Children's HospitalEimear E Kenny - Icahn School of Medicine at Mount SinaiDouglas P Kiel - Beth Israel Deaconess Medical CenterRobert Klemmer - University of MichiganBarbara A Konkle - University of WashingtonCharles Kooperberg - Fred Hutch Cancer CenterAnna Köttgen - Johns Hopkins UniversityLeslie A Lange - University of Colorado DenverJessica Lasky-Su - Brigham and Women's HospitalDaniel Levy - Boston UniversityXihong Lin - Harvard UniversityKeng-Han Lin - University of MichiganChunyu Liu - Boston UniversityRuth J F Loos - Icahn School of Medicine at Mount SinaiLori Garman - Oklahoma Medical Research FoundationRobert Gerszten - Beth Israel Deaconess Medical CenterSteven A Lubitz - Harvard UniversityKathryn L Lunetta - Boston UniversityAngel C Y Mak - University of California, San FranciscoAni Manichaikul - University of VirginiaAlisa K Manning - Broad InstituteRasika A Mathias - Johns Hopkins UniversityDavid D McManus - University of Massachusetts Chan Medical SchoolStephen T McGarvey - Brown UniversityJames B Meigs - Harvard UniversityDeborah A Meyers - University of ArizonaJulie L Mikulla - National Institutes of HealthMollie A Minear - National Institutes of HealthBraxton D Mitchell - University of Maryland, BaltimoreSanghamitra Mohanty - The University of Texas at AustinMay E Montasser - University of Maryland, BaltimoreCourtney Montgomery - Oklahoma Medical Research FoundationAlanna C Morrison - The University of Texas Health Science Center at HoustonJoanne M Murabito - Boston UniversityAndrea Natale - Texas Cardiac ArrhythmiaPradeep Natarajan - Massachusetts General HospitalSarah C Nelson - University of WashingtonKari E North - University of North Carolina at Chapel HillJeffrey R O'Connell - University of Maryland, BaltimoreNicholette D Palmer - Wake Forest UniversityNathan Pankratz - University of MinnesotaGina M Peloso - Boston UniversityPatricia A Peyser - University of MichiganJacob Pleiness - University of MichiganWendy S Post - Johns Hopkins UniversityBruce M Psaty - Kaiser Permanente Washington Health Research InstituteD C Rao - Washington University in St. LouisSusan Redline - Harvard UniversityAlexander P Reiner - University of WashingtonDan Roden - Vanderbilt University Medical CenterJerome I Rotter - The Lundquist InstituteIngo Ruczinski - Johns Hopkins UniversityChloé Sarnowski - Boston UniversitySebastian Schoenherr - Innsbruck Medical UniversityDavid A Schwartz - University of Colorado DenverJeong-Sun Seo - Seoul National University Bundang HospitalSudha Seshadri - The University of Texas at AustinVivien A Sheehan - Emory UniversityWayne H Sheu - Taichung Veterans General HospitalM Benjamin Shoemaker - Vanderbilt University Medical CenterNicholas L Smith - University of WashingtonJennifer A Smith - University of MichiganNona Sotoodehnia - University of WashingtonAdrienne M Stilp - University of WashingtonWeihong Tang - University of MinnesotaKent D Taylor - The Lundquist InstituteMarilyn Telen - Duke UniversityTimothy A Thornton - University of WashingtonRussell P Tracy - University of VermontDavid J Van Den Berg - University of Southern CaliforniaRamachandran S Vasan - Boston UniversityKarine A Viaud-Martinez - Illumina (United States)Scott Vrieze - University of MinnesotaDaniel E Weeks - University of PittsburghBruce S Weir - University of WashingtonScott T Weiss - Brigham and Women's HospitalLu-Chen Weng - Harvard UniversityCristen J Willer - University of MichiganYingze Zhang - University of PittsburghXutong Zhao - University of MichiganDonna K Arnett - University of KentuckyAllison E Ashley-Koch - Duke UniversityKathleen C Barnes - University of Colorado Anschutz Medical CampusEric Boerwinkle - Baylor College of MedicineStacey Gabriel - Broad InstituteRichard Gibbs - Baylor College of MedicineKenneth M Rice - University of WashingtonStephen S Rich - University of VirginiaEdwin K Silverman - Brigham and Women's HospitalPankaj Qasba - National Institutes of HealthWeiniu Gan - National Institutes of HealthGeorge J Papanicolaou - National Institutes of HealthDeborah A Nickerson - University of WashingtonSharon R Browning - University of WashingtonMichael C Zody - New York Genome CenterSebastian Zöllner - University of MichiganJames G Wilson - University of Mississippi Medical CenterL Adrienne Cupples - Boston UniversityCathy C Laurie - University of WashingtonCashell E Jaquish - National Institutes of HealthRyan D Hernandez - University of California, San FranciscoTimothy D O'Connor - Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA. timothydoconnor@gmail.comGonçalo R Abecasis - University of MichiganNHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
- Contributors
- Karin Hoth (Contributor) - University of Iowa, Psychiatry
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.590(7845), pp.290-299
- DOI
- 10.1038/s41586-021-03205-y
- PMID
- 33568819
- PMCID
- PMC7875770
- NLM abbreviation
- Nature
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Grant note
- K01 HL135405 / NHLBI NIH HHS R01 HL120393 / NHLBI NIH HHS R01 AI132476 / NIAID NIH HHS R21 HL123677 / NHLBI NIH HHS K01 AG059898 / NIA NIH HHS R01 DA037904 / NIDA NIH HHS R03 HL154284 / NHLBI NIH HHS UM1 DK078616 / NIDDK NIH HHS R01 HL149836 / NHLBI NIH HHS R01 HL142711 / NHLBI NIH HHS R01 HG005701 / NHGRI NIH HHS P30 ES010126 / NIEHS NIH HHS HHSN268201800001C / NHLBI NIH HHS UG3 HL151865 / NHLBI NIH HHS R01 HL117626 / NHLBI NIH HHS R01 HL155742 / NHLBI NIH HHS R01 HL113326 / NHLBI NIH HHS K24 HL148521 / NHLBI NIH HHS R01 HL141826 / NHLBI NIH HHS R01 HL131565 / NHLBI NIH HHS R01 DK117445 / NIDDK NIH HHS R35 HG010692 / NHGRI NIH HHS K08 HL141601 / NHLBI NIH HHS U01 HL120393 / NHLBI NIH HHS R01 HL123915 / NHLBI NIH HHS T32 HL007085 / NHLBI NIH HHS P50 HL118006 / NHLBI NIH HHS T32 HG000040 / NHGRI NIH HHS R03 HL141439 / NHLBI NIH HHS P30 DK020572 / NIDDK NIH HHS R01 MD012765 / NIMHD NIH HHS R01 DA044283 / NIDA NIH HHS
- Language
- English
- Date published
- 02/2021
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984293753802771
Metrics
20 Record Views