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Determinants of mosaic chromosomal alteration fitness.
Pershad, Yash; Mack, Taralynn; Poisner, Hannah; Jakubek, Yasminka A; Stilp, Adrienne M; Mitchell, Braxton D; Lewis, Joshua P; Boerwinkle, Eric; Loos, Ruth J F; Chami, Nathalie; Wang, Zhe; Barnes, Kathleen; Pankratz, Nathan; Fornage, Myriam; Redline, Susan; Psaty, Bruce M; Bis, Joshua C; Shojaie, Ali; Silverman, Edwin K; Cho, Michael H; Yun, Jeong H; DeMeo, Dawn; Levy, Daniel; Johnson, Andrew D; Mathias, Rasika A; Taub, Margaret A; Arnett, Donna; North, Kari E; Raffield, Laura M; Carson, April P; Doyle, Margaret F; Rich, Stephen S; Rotter, Jerome I; Guo, Xiuqing; Cox, Nancy J; Roden, Dan M; Franceschini, Nora; Desai, Pinkal; Reiner, Alex P; Auer, Paul L; Scheet, Paul A; Jaiswal, Siddhartha; Weinstock, Joshua S; Bick, Alexander G.
Affiliation
  • Pershad Y; Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, USA.
  • Mack T; Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, USA.
  • Poisner H; Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, USA.
  • Jakubek YA; Internal Medicine, Biomedical Informatics, University of Kentucky, Lexington, KY, USA.
  • Stilp AM; Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.
  • Mitchell BD; Dept of Medicine, Endocrinology, Diabetes, and Nutrition, University of Maryland, Baltimore, Baltimore, MD, USA.
  • Lewis JP; Dept of Medicine, Endocrinology, Diabetes, and Nutrition, University of Maryland, Baltimore, Baltimore, MD, 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.
  • Loos RJF; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Chami N; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Wang Z; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Barnes K; Division of Biomedical Informatics & Personalized Medicine, University of Colorado Anschutz, Aurora, CO, USA.
  • Pankratz N; Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN, USA.
  • Fornage M; 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.
  • Redline S; Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
  • Psaty BM; Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.
  • Bis JC; Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Systems and Population Health, University of Washington, Seattle, WA, USA.
  • Shojaie A; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
  • Silverman EK; Biostatistics, University of Washington, Seattle, WA, USA.
  • Cho MH; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Yun JH; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • DeMeo D; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Levy D; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Johnson AD; National Heart, Lung and Blood Institute, Population Sciences Branch, Framingham, MA, USA.
  • Mathias RA; National Heart, Lung and Blood Institute, Population Sciences Branch, Framingham, MA, USA.
  • Taub MA; Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MA, USA.
  • Arnett D; Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MA, USA.
  • North KE; Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
  • Raffield LM; Department of Epidemiology, University of North Carolina Chapel-Hill, Chapel Hill, NC, USA.
  • Carson AP; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Doyle MF; Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
  • Rich SS; Department of Pathology & Laboratory Medicine, The University of Vermont Larner College of Medicine, Colchester, VT, USA.
  • Rotter JI; Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, USA.
  • Guo X; Pediatrics, Genomic Outcomes, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Cox NJ; Pediatrics, Genomic Outcomes, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Roden DM; Division of Genetic Medicine, Department of Medicine, Vanderbilt University and Vanderbilt University Medical Center, Nashville, TN, USA.
  • Franceschini N; Departments of Medicine, Pharmacology, and Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Desai P; Department of Epidemiology, University of North Carolina Chapel-Hill, Chapel Hill, NC, USA.
  • Reiner AP; Weill Cornell Medical College, New York, NY, USA.
  • Auer PL; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Scheet PA; Division of Biostatistics, Insitute for Health & Equity and Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA.
  • Jaiswal S; Dept of Epidemiology, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
  • Weinstock JS; Department of Pathology, Stanford University, Stanford, CA, USA.
  • Bick AG; Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Nat Commun ; 15(1): 3800, 2024 May 07.
Article in En | MEDLINE | ID: mdl-38714703
ABSTRACT
Clonal hematopoiesis (CH) is characterized by the acquisition of a somatic mutation in a hematopoietic stem cell that results in a clonal expansion. These driver mutations can be single nucleotide variants in cancer driver genes or larger structural rearrangements called mosaic chromosomal alterations (mCAs). The factors that influence the variations in mCA fitness and ultimately result in different clonal expansion rates are not well understood. We used the Passenger-Approximated Clonal Expansion Rate (PACER) method to estimate clonal expansion rate as PACER scores for 6,381 individuals in the NHLBI TOPMed cohort with gain, loss, and copy-neutral loss of heterozygosity mCAs. Our mCA fitness estimates, derived by aggregating per-individual PACER scores, were correlated (R2 = 0.49) with an alternative approach that estimated fitness of mCAs in the UK Biobank using population-level distributions of clonal fraction. Among individuals with JAK2 V617F clonal hematopoiesis of indeterminate potential or mCAs affecting the JAK2 gene on chromosome 9, PACER score was strongly correlated with erythrocyte count. In a cross-sectional analysis, genome-wide association study of estimates of mCA expansion rate identified a TCL1A locus variant associated with mCA clonal expansion rate, with suggestive variants in NRIP1 and TERT.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Chromosome Aberrations / Clonal Hematopoiesis / Mosaicism Limits: Aged / Female / Humans / Male / Middle aged Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2024 Document type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Chromosome Aberrations / Clonal Hematopoiesis / Mosaicism Limits: Aged / Female / Humans / Male / Middle aged Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2024 Document type: Article Affiliation country: United States