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

dc.contributor.authorTaliun, Daniel
dc.contributor.authorHarris, Daniel N.
dc.contributor.authorKessler, Michael D.
dc.contributor.authorCarlson, Jedidiah
dc.contributor.authorSzpiech, Zachary A.
dc.contributor.authorTorres, Raul
dc.contributor.authorGagliano Taliun, Sarah A.
dc.contributor.authorCorvelo, André
dc.contributor.authorGogarten, Stephanie M.
dc.contributor.authorKang, Hyun Min
dc.contributor.authorPitsillides, Achilleas N.
dc.contributor.authorLeFaive, Jonathon
dc.contributor.authorLee, Seung-Been
dc.contributor.authorTian, Xiaowen
dc.contributor.authorBrowning, Brian L.
dc.contributor.authorDas, Sayantan
dc.contributor.authorEmde, Anne-Katrin
dc.contributor.authorClarke, Wayne E.
dc.contributor.authorLoesch, Douglas P.
dc.contributor.authorShetty, Amol C.
dc.contributor.authorBlackwell, Thomas W.
dc.contributor.authorSmith, Albert V.
dc.contributor.authorWong, Quenna
dc.contributor.authorLiu, Xiaoming
dc.contributor.authorConomos, Matthew P.
dc.contributor.authorBobo, Dean M.
dc.contributor.authorAguet, François
dc.contributor.authorAlbert, Christine
dc.contributor.authorAlonso, Alvaro
dc.contributor.authorArdlie, Kristin G.
dc.contributor.authorArking, Dan E.
dc.contributor.authorAslibekyan, Stella
dc.contributor.authorAuer, Paul L.
dc.contributor.authorBarnard, John
dc.contributor.authorBarr, R. Graham
dc.contributor.authorBarwick, Lucas
dc.contributor.authorBecker, Lewis C.
dc.contributor.authorBeer, Rebecca L.
dc.contributor.authorBenjamin, Emelia J.
dc.contributor.authorBielak, Lawrence F.
dc.contributor.authorBlangero, John
dc.contributor.authorBoehnke, Michael
dc.contributor.authorBowden, Donald W.
dc.contributor.authorBrody, Jennifer A.
dc.contributor.authorBurchard, Esteban G.
dc.contributor.authorCade, Brian E.
dc.contributor.authorCasella, James F.
dc.contributor.authorChalazan, Brandon
dc.contributor.authorChasman, Daniel I.
dc.contributor.authorChen, Yii-Der Ida
dc.contributor.authorCho, Michael H.
dc.contributor.authorChoi, Seung Hoan
dc.contributor.authorChung, Mina K.
dc.contributor.authorClish, Clary B.
dc.contributor.authorCorrea, Adolfo
dc.contributor.authorCurran, Joanne E.
dc.contributor.authorCuster, Brian
dc.contributor.authorDarbar, Dawood
dc.contributor.authorDaya, Michelle
dc.contributor.authorde Andrade, Mariza
dc.contributor.authorDeMeo, Dawn L.
dc.contributor.authorDutcher, Susan K.
dc.contributor.authorEllinor, Patrick T.
dc.contributor.authorEmery, Leslie S.
dc.contributor.authorEng, Celeste
dc.contributor.authorFatkin, Diane
dc.contributor.authorFingerlin, Tasha
dc.contributor.authorForer, Lukas
dc.contributor.authorFornage, Myriam
dc.contributor.authorFranceschini, Nora
dc.contributor.authorFuchsberger, Christian
dc.contributor.authorFullerton, Stephanie M.
dc.contributor.authorGermer, Soren
dc.contributor.authorGladwin, Mark T.
dc.contributor.authorGottlieb, Daniel J.
dc.contributor.authorGuo, Xiuqing
dc.contributor.authorHall, Michael E.
dc.contributor.authorHe, Jiang
dc.contributor.authorHeard-Costa, Nancy L.
dc.contributor.authorHeckbert, Susan R.
dc.contributor.authorIrvin, Marguerite R.
dc.contributor.authorJohnsen, Jill M.
dc.contributor.authorJohnson, Andrew D.
dc.contributor.authorKaplan, Robert
dc.contributor.authorKardia, Sharon L. R.
dc.contributor.authorKelly, Tanika
dc.contributor.authorKelly, Shannon
dc.contributor.authorKenny, Eimear E.
dc.contributor.authorKiel, Douglas P.
dc.contributor.authorKlemmer, Robert
dc.contributor.authorKonkle, Barbara A.
dc.contributor.authorKooperberg, Charles
dc.contributor.authorKöttgen, Anna
dc.contributor.authorLange, Leslie A.
dc.contributor.authorLasky-Su, Jessica
dc.contributor.authorLevy, Daniel
dc.contributor.authorLin, Xihong
dc.contributor.authorLin, Keng-Han
dc.contributor.authorLiu, Chunyu
dc.contributor.authorLoos, Ruth J. F.
dc.contributor.authorGarman, Lori
dc.contributor.authorGerszten, Robert
dc.contributor.authorLubitz, Steven A.
dc.contributor.authorLunetta, Kathryn L.
dc.contributor.authorMak, Angel C. Y.
dc.contributor.authorManichaikul, Ani
dc.contributor.authorManning, Alisa K.
dc.contributor.authorMathias, Rasika A.
dc.contributor.authorMcManus, David D.
dc.contributor.authorMcGarvey, Stephen T.
dc.contributor.authorMeigs, James B.
dc.contributor.authorMeyers, Deborah A.
dc.contributor.authorMikulla, Julie L.
dc.contributor.authorMinear, Mollie A.
dc.contributor.authorMitchell, Braxton D.
dc.contributor.authorMohanty, Sanghamitra
dc.contributor.authorMontasser, May E.
dc.contributor.authorMontgomery, Courtney
dc.contributor.authorMorrison, Alanna C.
dc.contributor.authorMurabito, Joanne M.
dc.contributor.authorNatale, Andrea
dc.contributor.authorNatarajan, Pradeep
dc.contributor.authorNelson, Sarah C.
dc.contributor.authorNorth, Kari E.
dc.contributor.authorO'Connell, Jeffrey R.
dc.contributor.authorPalmer, Nicholette D.
dc.contributor.authorPankratz, Nathan
dc.contributor.authorPeloso, Gina M.
dc.contributor.authorPeyser, Patricia A.
dc.contributor.authorPleiness, Jacob
dc.contributor.authorPost, Wendy S.
dc.contributor.authorPsaty, Bruce M.
dc.contributor.authorRao, D. C.
dc.contributor.authorRedline, Susan
dc.contributor.authorReiner, Alexander P.
dc.contributor.authorRoden, Dan
dc.contributor.authorRotter, Jerome I.
dc.contributor.authorRuczinski, Ingo
dc.contributor.authorSarnowski, Chloé
dc.contributor.authorSchoenherr, Sebastian
dc.contributor.authorSchwartz, David A.
dc.contributor.authorSeo, Jeong-Sun
dc.contributor.authorSeshadri, Sudha
dc.contributor.authorSheehan, Vivien A.
dc.contributor.authorSheu, Wayne H.
dc.contributor.authorShoemaker, M. Benjamin
dc.contributor.authorSmith, Nicholas L.
dc.contributor.authorSmith, Jennifer A.
dc.contributor.authorSotoodehnia, Nona
dc.contributor.authorStilp, Adrienne M.
dc.contributor.authorTang, Weihong
dc.contributor.authorTaylor, Kent D.
dc.contributor.authorTelen, Marilyn
dc.contributor.authorThornton, Timothy A.
dc.contributor.authorTracy, Russell P.
dc.contributor.authorVan Den Berg, David J.
dc.contributor.authorVasan, Ramachandran S.
dc.contributor.authorViaud-Martinez, Karine A.
dc.contributor.authorVrieze, Scott
dc.contributor.authorWeeks, Daniel E.
dc.contributor.authorWeir, Bruce S.
dc.contributor.authorWeiss, Scott T.
dc.contributor.authorWeng, Lu-Chen
dc.contributor.authorWiller, Cristen J.
dc.contributor.authorZhang, Yingze
dc.contributor.authorZhao, Xutong
dc.contributor.authorArnett, Donna K.
dc.contributor.authorAshley-Koch, Allison E.
dc.contributor.authorBarnes, Kathleen C.
dc.contributor.authorBoerwinkle, Eric
dc.contributor.authorGabriel, Stacey
dc.contributor.authorGibbs, Richard
dc.contributor.authorRice, Kenneth M.
dc.contributor.authorRich, Stephen S.
dc.contributor.authorSilverman, Edwin K.
dc.contributor.authorQasba, Pankaj
dc.contributor.authorGan, Weiniu
dc.contributor.authorNHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
dc.contributor.authorPapanicolaou, George J.
dc.contributor.authorNickerson, Deborah A.
dc.contributor.authorBrowning, Sharon R.
dc.contributor.authorZody, Michael C.
dc.contributor.authorZöllner, Sebastian
dc.contributor.authorWilson, James G.
dc.contributor.authorCupples, L. Adrienne
dc.contributor.authorLaurie, Cathy C.
dc.contributor.authorJaquish, Cashell E.
dc.contributor.authorHernandez, Ryan D.
dc.contributor.authorO'Connor, Timothy D.
dc.contributor.authorAbecasis, Gonçalo R.
dc.contributor.departmentEpidemiology, Richard M. Fairbanks School of Public Health
dc.date.accessioned2024-08-12T17:03:34Z
dc.date.available2024-08-12T17:03:34Z
dc.date.issued2021
dc.description.abstractThe 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%.
dc.eprint.versionFinal published version
dc.identifier.citationTaliun D, Harris DN, Kessler MD, et al. Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program. Nature. 2021;590(7845):290-299. doi:10.1038/s41586-021-03205-y
dc.identifier.urihttps://hdl.handle.net/1805/42739
dc.language.isoen_US
dc.publisherSpringer Nature
dc.relation.isversionof10.1038/s41586-021-03205-y
dc.relation.journalNature
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourcePMC
dc.subjectRare variants
dc.subjectNext-generation sequencing
dc.subjectGenetics research
dc.titleSequencing of 53,831 diverse genomes from the NHLBI TOPMed Program
dc.typeArticle
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