Taliun, Daniel and Harris, Daniel N. and Kessler, Michael D. and Carlson, Jedidiah and Szpiech, Zachary A. and Torres, Raul and Taliun, Sarah A. Gagliano and Corvelo, André and Gogarten, Stephanie M. and Kang, Hyun Min and Pitsillides, Achilleas N. and LeFaive, Jonathon and Lee, Seung-been and Tian, Xiaowen and Browning, Brian L. and Das, Sayantan and Emde, Anne-Katrin and Clarke, Wayne E. and Loesch, Douglas P. and Shetty, Amol C. and Blackwell, Thomas W. and Smith, Albert V. and Wong, Quenna and Liu, Xiaoming and Conomos, Matthew P. and Bobo, Dean M. and Aguet, François and Albert, Christine and Alonso, Alvaro and Ardlie, Kristin G. and Arking, Dan E. and Aslibekyan, Stella and Auer, Paul L. and Barnard, John and Barr, R. Graham and Barwick, Lucas and Becker, Lewis C. and Beer, Rebecca L. and Benjamin, Emelia J. and Bielak, Lawrence F. and Blangero, John and Boehnke, Michael and Bowden, Donald W. and Brody, Jennifer A. and Burchard, Esteban G. and Cade, Brian E. and Casella, James F. and Chalazan, Brandon and Chasman, Daniel I. and Chen, Yii-Der Ida and Cho, Michael H. and Choi, Seung Hoan and Chung, Mina K. and Clish, Clary B. and Correa, Adolfo and Curran, Joanne E. and Custer, Brian and Darbar, Dawood and Daya, Michelle and de Andrade, Mariza and DeMeo, Dawn L. and Dutcher, Susan K. and Ellinor, Patrick T. and Emery, Leslie S. and Eng, Celeste and Fatkin, Diane and Fingerlin, Tasha and Forer, Lukas and Fornage, Myriam and Franceschini, Nora and Fuchsberger, Christian and Fullerton, Stephanie M. and Germer, Soren and Gladwin, Mark T. and Gottlieb, Daniel J. and Guo, Xiuqing and Hall, Michael E. and He, Jiang and Heard-Costa, Nancy L. and Heckbert, Susan R. and Irvin, Marguerite R. and Johnsen, Jill M. and Johnson, Andrew D. and Kaplan, Robert and Kardia, Sharon L. R. and Kelly, Tanika and Kelly, Shannon and Kenny, Eimear E. and Kiel, Douglas P. and Klemmer, Robert and Konkle, Barbara A. and Kooperberg, Charles and Köttgen, Anna and Lange, Leslie A. and Lasky-Su, Jessica and Levy, Daniel and Lin, Xihong and Lin, Keng-Han and Liu, Chunyu and Loos, Ruth J. F. and Garman, Lori and Gerszten, Robert and Lubitz, Steven A. and Lunetta, Kathryn L. and Mak, Angel C. Y. and Manichaikul, Ani and Manning, Alisa K. and Mathias, Rasika A. and McManus, David D. and McGarvey, Stephen T. and Meigs, James B. and Meyers, Deborah A. and Mikulla, Julie L. and Minear, Mollie A. and Mitchell, Braxton D. and Mohanty, Sanghamitra and Montasser, May E. and Montgomery, Courtney and Morrison, Alanna C. and Murabito, Joanne M. and Natale, Andrea and Natarajan, Pradeep and Nelson, Sarah C. and North, Kari E. and O’Connell, Jeffrey R. and Palmer, Nicholette D. and Pankratz, Nathan and Peloso, Gina M. and Peyser, Patricia A. and Pleiness, Jacob and Post, Wendy S. and Psaty, Bruce M. and Rao, D. C. and Redline, Susan and Reiner, Alexander P. and Roden, Dan and Rotter, Jerome I. and Ruczinski, Ingo and Sarnowski, Chloé and Schoenherr, Sebastian and Schwartz, David A. and Seo, Jeong-Sun and Seshadri, Sudha and Sheehan, Vivien A. and Sheu, Wayne H. and Shoemaker, M. Benjamin and Smith, Nicholas L. and Smith, Jennifer A. and Sotoodehnia, Nona and Stilp, Adrienne M. and Tang, Weihong and Taylor, Kent D. and Telen, Marilyn and Thornton, Timothy A. and Tracy, Russell P. and Van Den Berg, David J. and Vasan, Ramachandran S. and Viaud-Martinez, Karine A. and Vrieze, Scott and Weeks, Daniel E. and Weir, Bruce S. and Weiss, Scott T. and Weng, Lu-Chen and Willer, Cristen J. and Zhang, Yingze and Zhao, Xutong and Arnett, Donna K. and Ashley-Koch, Allison E. and Barnes, Kathleen C. and Boerwinkle, Eric and Gabriel, Stacey and Gibbs, Richard and Rice, Kenneth M. and Rich, Stephen S. and Silverman, Edwin K. and Qasba, Pankaj and Gan, Weiniu and Papanicolaou, George J. and Nickerson, Deborah A. and Browning, Sharon R. and Zody, Michael C. and Zöllner, Sebastian and Wilson, James G. and Cupples, L. Adrienne and Laurie, Cathy C. and Jaquish, Cashell E. and Hernandez, Ryan D. and O’Connor, Timothy D. and Abecasis, Gonçalo R. (2021) Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program. Nature, 590 (7845). pp.290-299. ISSN 0028-0836
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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%.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 15 Mar 2021 22:59 |
| Last Modified: | 01 Aug 2021 04:46 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/1053 |
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