| Literature DB >> 33568819 |
Daniel Taliun1,2, Daniel N Harris3,4,5, Michael D Kessler3,4,5, Jedidiah Carlson6,7, Zachary A Szpiech8,9, Raul Torres10, Sarah A Gagliano Taliun1,2, André Corvelo11, Stephanie M Gogarten12, Hyun Min Kang1,2, Achilleas N Pitsillides13, Jonathon LeFaive1,2, Seung-Been Lee7, Xiaowen Tian12, Brian L Browning14, Sayantan Das1,2, Anne-Katrin Emde11, Wayne E Clarke11, Douglas P Loesch3,4,5, Amol C Shetty3,4,5, Thomas W Blackwell1,2, Albert V Smith1,2, Quenna Wong12, Xiaoming Liu15, Matthew P Conomos12, Dean M Bobo16, François Aguet17, Christine Albert18, Alvaro Alonso19, Kristin G Ardlie17, Dan E Arking20, Stella Aslibekyan21, Paul L Auer22, John Barnard23, R Graham Barr24,25, Lucas Barwick26, Lewis C Becker27, Rebecca L Beer28, Emelia J Benjamin29,30,31, Lawrence F Bielak32, John Blangero33,34, Michael Boehnke1,2, Donald W Bowden35, Jennifer A Brody36,37, Esteban G Burchard38,39, Brian E Cade40,41, James F Casella42,43, Brandon Chalazan44, Daniel I Chasman45,46, Yii-Der Ida Chen47, Michael H Cho48, Seung Hoan Choi17, Mina K Chung49,50,51, Clary B Clish52, Adolfo Correa53,54,55, Joanne E Curran33,34, Brian Custer56,57, Dawood Darbar58, Michelle Daya59, Mariza de Andrade60, Dawn L DeMeo48, Susan K Dutcher61,62, Patrick T Ellinor63, Leslie S Emery12, Celeste Eng39, Diane Fatkin64,65,66, Tasha Fingerlin67, Lukas Forer68, Myriam Fornage69, Nora Franceschini70, Christian Fuchsberger1,2,68,71, Stephanie M Fullerton72, Soren Germer11, Mark T Gladwin73,74,75, Daniel J Gottlieb76,77, Xiuqing Guo47, Michael E Hall53, Jiang He78,79, Nancy L Heard-Costa31,80, Susan R Heckbert37,81, Marguerite R Irvin82, Jill M Johnsen36,83, Andrew D Johnson31,84, Robert Kaplan85, Sharon L R Kardia32, Tanika Kelly78, Shannon Kelly86,87,88, Eimear E Kenny16, Douglas P Kiel17,40,89,90, Robert Klemmer1,2, Barbara A Konkle36,83, Charles Kooperberg91, Anna Köttgen92,93, Leslie A Lange94, Jessica Lasky-Su40,41,48,95, Daniel Levy29,31,84, Xihong Lin96, Keng-Han Lin1,2, Chunyu Liu13, Ruth J F Loos97,98, Lori Garman99, Robert Gerszten100, Steven A Lubitz18, Kathryn L Lunetta13, Angel C Y Mak39, Ani Manichaikul101,102, Alisa K Manning40,103,104, Rasika A Mathias105, David D McManus106, Stephen T McGarvey107,108,109, James B Meigs110, Deborah A Meyers111, Julie L Mikulla28, Mollie A Minear28, Braxton D Mitchell4,5,112, Sanghamitra Mohanty113,114, May E Montasser4,5, Courtney Montgomery99, Alanna C Morrison115, Joanne M Murabito29, Andrea Natale113, Pradeep Natarajan40,63,116,117, Sarah C Nelson12, Kari E North70, Jeffrey R O'Connell4,5, Nicholette D Palmer35, Nathan Pankratz118, Gina M Peloso13, Patricia A Peyser32, Jacob Pleiness1,2, Wendy S Post119, Bruce M Psaty36,37,81,120,121, D C Rao122, Susan Redline40,41, Alexander P Reiner81,91, Dan Roden123, Jerome I Rotter47, Ingo Ruczinski124, Chloé Sarnowski13, Sebastian Schoenherr68, David A Schwartz125, Jeong-Sun Seo126,127,128, Sudha Seshadri31,129, Vivien A Sheehan130,131, Wayne H Sheu132, M Benjamin Shoemaker123, Nicholas L Smith81,121,133, Jennifer A Smith32,134, Nona Sotoodehnia37, Adrienne M Stilp12, Weihong Tang135, Kent D Taylor47, Marilyn Telen136, Timothy A Thornton12, Russell P Tracy137, David J Van Den Berg138, Ramachandran S Vasan29,31, Karine A Viaud-Martinez139, Scott Vrieze140, Daniel E Weeks141,142, Bruce S Weir12, Scott T Weiss40,41,48,95, Lu-Chen Weng18, Cristen J Willer6,143,144, Yingze Zhang73,74,75, Xutong Zhao1,2, Donna K Arnett145, Allison E Ashley-Koch146, Kathleen C Barnes59, Eric Boerwinkle147,148, Stacey Gabriel17, Richard Gibbs148, Kenneth M Rice12, Stephen S Rich101,102, Edwin K Silverman48, Pankaj Qasba28, Weiniu Gan28, George J Papanicolaou28, Deborah A Nickerson7,149,150, Sharon R Browning12, Michael C Zody11, Sebastian Zöllner1,2,151, James G Wilson152, L Adrienne Cupples153,154, Cathy C Laurie155, Cashell E Jaquish156, Ryan D Hernandez157,158,159,160,161, Timothy D O'Connor162,163,164, Gonçalo R Abecasis165.
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%.Entities:
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Year: 2021 PMID： 33568819 PMCID： PMC7875770 DOI： 10.1038/s41586-021-03205-y
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 69.504