Structural variation across 138,134 samples in the TOPMed consortium.

Autor: Jun G; Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston., English AC; Baylor College of Medicine Human Genome Sequencing Center, Houston, TX, USA., Metcalf GA; Baylor College of Medicine Human Genome Sequencing Center, Houston, TX, USA., Yang J; University of Southern California, Los Angeles, CA, USA., Chaisson MJ; University of Southern California, Los Angeles, CA, USA., Pankratz N; University of Minnesota, Minneapolis, MN, USA., Menon VK; Baylor College of Medicine Human Genome Sequencing Center, Houston, TX, USA., Salerno WJ; Regeneron Genetics Center., Krasheninina O; Regeneron Genetics Center., Smith AV; Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI., Lane JA; Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI., Blackwell T; Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI., Kang HM; Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI., Salvi S; Baylor College of Medicine Human Genome Sequencing Center, Houston, TX, USA., Meng Q; Baylor College of Medicine Human Genome Sequencing Center, Houston, TX, USA., Shen H; Baylor College of Medicine Human Genome Sequencing Center, Houston, TX, USA., Pasham D; Baylor College of Medicine Human Genome Sequencing Center, Houston, TX, USA., Bhamidipati S; Baylor College of Medicine Human Genome Sequencing Center, Houston, TX, USA., Kottapalli K; Baylor College of Medicine Human Genome Sequencing Center, Houston, TX, USA., Arnett DK; Department of Epidemiology, University of Kentucky College of Public Health., Ashley-Koch A; Department of Medicine, Duke University Medical Center, Durham, NC.; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC., Auer PL; Division of Biostatistics and Cancer Center, Medical College of Wisconsin, Milwaukee WI., Beutel KM; University of Minnesota, Minneapolis, MN, USA., Bis JC; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA., Blangero J; Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas, Rio Grande Valley School of Medicine, Brownsville, TX., Bowden DW; Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA., Brody JA; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA., Cade BE; Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA., Chen YI; Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center.; The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA USA., Cho MH; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA., Curran JE; Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA., Fornage M; Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX., Freedman BI; Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC, USA., Fingerlin T; Center for Genes, Environment and Health, National Jewish Health, 1400 Jackson St., Denver, CO, 80206, USA., Gelb BD; Mindich Child Health and Development Institute and the Departments of Pediatrics and Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai., Hou L; Northwestern University, Chicago, IL., Hung YJ; Institute of Preventive Medicine, National Defense Medical Center, Taiwan., Kane JP; Cardiovascular Research Institute, University of California, San Francisco., Kaplan R; Department of epidemiology and population health, Albert Einstein College of Medicine, Bronx NY USA., Kim W; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA., Loos RJF; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY., Marcus GM; Division of Cardiology, University of California, San Francisco CA., Mathias RA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD., McGarvey ST; Department of Epidemiology, International Health Institute and Department of Anthropology, Brown University., Montgomery C; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation., Naseri T; Ministry of Health, Government of Samoa, Apia, Samoa., Nouraie SM; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213., Preuss MH; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY., Palmer ND; Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA., Peyser PA; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI USA., Raffield LM; Department of Genetics, University of North Carolina at Chapel Hill., Ratan A; Center for Public Health Genomics, University of Virginia, Charlottesville, VA USA., Redline S; Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA., Reupena S; Lutia i Puava ae Mapu i Fagalele, Apia, Samoa 663030., Rotter JI; The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA USA.; Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Rich SS; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI USA., Rienstra M; Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Ruczinski I; Department of Biostatistics, Johns Hopkins University Bloomberg, School of Public Health, Baltimore, MD, USA., Sankaran VG; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.; Broad Institute of MIT and Harvard, Cambridge, MA 02142., Schwartz DA; University of Colorado Department of Medicine., Seidman CE; Department of Genetics, Harvard Medical School.; Cardiovascular Division, Brigham & Women's Hospital, Harvard University.; Howard Hughes Medical Institute, Harvard University., Seidman JG; Department of Genetics, Harvard Medical School., Silverman EK; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA., Smith JA; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213., Stilp A; Department of Biostatistics, University of Washington, Seattle, WA., Taylor KD; The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA USA.; Center for Public Health Genomics, University of Virginia, Charlottesville, VA USA., Telen MJ; Department of Medicine, Duke University Medical Center, Durham, NC., Weiss ST; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA., Williams LK; Center for Individualized and Genomic Medicine Research (CIGMA), Department of Internal Medicine, Henry Ford Health System, Detroit, Michigan, United States of America., Wu B; Center for Individualized and Genomic Medicine Research (CIGMA), Department of Internal Medicine, Henry Ford Health System, Detroit, Michigan, United States of America., Yanek LR; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY., Zhang Y; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213., Lasky-Su J; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA., Gingras MC; Baylor College of Medicine Human Genome Sequencing Center, Houston, TX, USA., Dutcher SK; Department of Genetics, Washington University School of Medicine, Saint Louis, MO 63110, USA., Eichler EE; Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington, USA.; Howard Hughes Medical Institute, University of Washington, Seattle, Washington, USA., Gabriel S; Broad Institute of MIT and Harvard, Cambridge, MA 02142., Germer S; New York Genome Center, New York, NY, USA., Kim R; Psomagen, Inc.,Rockville, Maryland, USA., Viaud-Martinez KA; Illumina Laboratory Services, Illumina, Inc., San Diego., Nickerson DA; Department of Genome Sciences, University of Washington, Seattle, WA 98195., Luo J; National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA., Reiner A; Department of Epidemiology, University of Washington, Seattle, WA 98109, USA., Gibbs RA; Baylor College of Medicine Human Genome Sequencing Center, Houston, TX, USA., Boerwinkle E; Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston.; Baylor College of Medicine Human Genome Sequencing Center, Houston, TX, USA., Abecasis G; Regeneron Genetics Center.; Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI., Sedlazeck FJ; Baylor College of Medicine Human Genome Sequencing Center, Houston, TX, USA.; Department of Computer Science, Rice University, 6100 Main Street, Houston, TX, 77005, USA.
Jazyk: angličtina
Zdroj: Research square [Res Sq] 2023 Feb 03. Date of Electronic Publication: 2023 Feb 03.
DOI: 10.21203/rs.3.rs-2515453/v1
Abstrakt: Ever larger Structural Variant (SV) catalogs highlighting the diversity within and between populations help researchers better understand the links between SVs and disease. The identification of SVs from DNA sequence data is non-trivial and requires a balance between comprehensiveness and precision. Here we present a catalog of 355,667 SVs (59.34% novel) across autosomes and the X chromosome (50bp+) from 138,134 individuals in the diverse TOPMed consortium. We describe our methodologies for SV inference resulting in high variant quality and >90% allele concordance compared to long-read de-novo assemblies of well-characterized control samples. We demonstrate utility through significant associations between SVs and important various cardio-metabolic and hematologic traits. We have identified 690 SV hotspots and deserts and those that potentially impact the regulation of medically relevant genes. This catalog characterizes SVs across multiple populations and will serve as a valuable tool to understand the impact of SV on disease development and progression.
Databáze: MEDLINE