Mosaic chromosomal alterations in blood across ancestries using whole-genome sequencing.

Autor: Jakubek YA; Department of Internal Medicine, University of Kentucky, Lexington, KY, USA., Zhou Y; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Stilp A; Department of Biostatistics, University of Washington, Seattle, WA, USA., Bacon J; Department of Computer Science, Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI, USA., Wong JW; Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA., Ozcan Z; Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA., Arnett D; University of South Carolina, Columbia, SC, USA., Barnes K; Division of Biomedical Informatics and Personalized Medicine, School of Medicine University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Bis JC; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA., Boerwinkle E; Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA., Brody JA; Cardiovascular Health Research Unit, Department of Medicine, University of Washington Seattle, Seattle, WA, USA., Carson AP; Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA., Chasman DI; Brigham and Women's Hospital, Boston, MA, USA., Chen J; Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Cho M; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA., Conomos MP; Department of Biostatistics, University of Washington, Seattle, WA, USA., Cox N; Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Doyle MF; Department of Pathology and Laboratory Medicine, The University of Vermont Larner College of Medicine, Colchester, VT, USA., Fornage M; University of Texas Health Science Center at Houston, Houston, TX, USA., Guo X; 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., Kardia SLR; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA., Lewis JP; Department of Medicine, University of Maryland Baltimore, Baltimore, MD, USA., Loos RJF; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Ma X; Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA., Machiela MJ; National Institutes of Health, Bethesda, MD, USA., Mack TM; Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Mathias RA; Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MA, USA., Mitchell BD; Department of Medicine, University of Maryland Baltimore, Baltimore, MD, USA., Mychaleckyj JC; Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA., North K; Department of Epidemiology, University of North Carolina Chapel-Hill, Chapel Hill, NC, USA., Pankratz N; Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN, USA., Peyser PA; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA., Preuss MH; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Psaty B; Cardiovascular Health Research Unit, Department of Medicine, Department of Epidemiology, Department of Health Systems and Population Health, University of Washington, Seattle, WA, USA., Raffield LM; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Vasan RS; Department of Epidemiology, Boston University, Boston, MA, USA., Redline S; Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA., Rich SS; Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA., 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., Silverman EK; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA., Smith JA; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.; Institute for Social Research, Survey Research Center, University of Michigan, Ann Arbor, MI, USA., Smith AP; Institute for Biomedical Informatics, University of Kentucky, Lexington, KY, USA., Taub M; Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MA, USA., 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., Yun J; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA., Li Y; Department of Biostatistics, Department of Genetics, Department of Computer Science, University of North Carolina Chapel-Hill, Chapel Hill, NC, USA., Desai P; Department of Medicine, Weill Cornell Medicine, New York, NY, USA., Bick AG; Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Reiner AP; Department of Epidemiology, University of Washington, Seattle, WA, USA., Scheet P; Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. PAScheet@mdanderson.org., Auer PL; Division of Biostatistics, Institute for Health and Equity, and Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA. pauer@mcw.edu.
Jazyk: angličtina
Zdroj: Nature genetics [Nat Genet] 2023 Nov; Vol. 55 (11), pp. 1912-1919. Date of Electronic Publication: 2023 Oct 30.
DOI: 10.1038/s41588-023-01553-1
Abstrakt: Megabase-scale mosaic chromosomal alterations (mCAs) in blood are prognostic markers for a host of human diseases. Here, to gain a better understanding of mCA rates in genetically diverse populations, we analyzed whole-genome sequencing data from 67,390 individuals from the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program. We observed higher sensitivity with whole-genome sequencing data, compared with array-based data, in uncovering mCAs at low mutant cell fractions and found that individuals of European ancestry have the highest rates of autosomal mCAs and the lowest rates of chromosome X mCAs, compared with individuals of African or Hispanic ancestry. Although further studies in diverse populations will be needed to replicate our findings, we report three loci associated with loss of chromosome X, associations between autosomal mCAs and rare variants in DCPS, ADM17, PPP1R16B and TET2 and ancestry-specific variants in ATM and MPL with mCAs in cis.
(© 2023. The Author(s).)
Databáze: MEDLINE
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