Portal de Periódicos da CAPES

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

2019; Cold Spring Harbor Laboratory; Linguagem: Inglês

10.1101/563866

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

Genetic factors in colorectal cancer

Summary paragraph The Trans-Omics for Precision Medicine (TOPMed) program seeks to elucidate the genetic architecture and disease biology of heart, lung, blood, and sleep disorders, with the ultimate goal of improving diagnosis, treatment, and prevention. The initial phases of the program focus on whole genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here, we describe TOPMed goals and design as well as resources and early insights from the sequence data. The resources include a variant browser, a genotype imputation panel, and sharing of genomic and phenotypic data via dbGaP. In 53,581 TOPMed samples, >400 million single-nucleotide and insertion/deletion variants were detected by alignment with the reference genome. Additional novel variants are detectable through assembly of unmapped reads and customized analysis in highly variable loci. Among the >400 million variants detected, 97% have frequency <1% and 46% are singletons. These rare variants provide insights into mutational processes and recent human evolutionary history. The nearly complete catalog of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and non-coding sequence variants to phenotypic variation. Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and extends the reach of nearly all genome-wide association studies to include variants down to ~0.01% in frequency.