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Epigenetic and proteomic signatures associate with clonal hematopoiesis expansion rate.
Mack, Taralynn M; Raddatz, Michael A; Pershad, Yash; Nachun, Daniel C; Taylor, Kent D; Guo, Xiuqing; Shuldiner, Alan R; O'Connell, Jeffrey R; Kenny, Eimear E; Loos, Ruth J F; Redline, Susan; Cade, Brian E; Psaty, Bruce M; Bis, Joshua C; Brody, Jennifer A; Silverman, Edwin K; Yun, Jeong H; Cho, Michael H; DeMeo, Dawn L; Levy, Daniel; Johnson, Andrew D; Mathias, Rasika A; Yanek, Lisa R; Heckbert, Susan R; Smith, Nicholas L; Wiggins, Kerri L; Raffield, Laura M; Carson, April P; Rotter, Jerome I; Rich, Stephen S; Manichaikul, Ani W; Gu, C Charles; Chen, Yii-Der Ida; Lee, Wen-Jane; Shoemaker, M Benjamin; Roden, Dan M; Kooperberg, Charles; Auer, Paul L; Desai, Pinkal; Blackwell, Thomas W; Smith, Albert V; Reiner, Alexander P; Jaiswal, Siddhartha; Weinstock, Joshua S; Bick, Alexander G.
Afiliação
  • Mack TM; Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Raddatz MA; Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Pershad Y; Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Nachun DC; Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Taylor KD; Department of Pathology, Stanford University, Stanford, CA, 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.
  • Shuldiner AR; 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.
  • O'Connell JR; Department of Medicine, University of Maryland, Baltimore, Baltimore, MD, USA.
  • Kenny EE; Department of Medicine, University of Maryland, Baltimore, Baltimore, MD, USA.
  • Loos RJF; Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Redline S; The Charles Bronfman Institute of Personalized Medicine, Mount Sinai Hospital, New York City, NY, USA.
  • Cade BE; The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Psaty BM; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Bis JC; Harvard Medical School, Boston, MA, USA.
  • Brody JA; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Silverman EK; Harvard Medical School, Boston, MA, USA.
  • Yun JH; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Cho MH; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
  • DeMeo DL; Department of Epidemiology, University of Washington, Seattle, WA, USA.
  • Levy D; Department of Medicine, University of Washington, Seattle, WA, USA.
  • Johnson AD; Department of Health Systems and Population Health, University of Washington, Seattle, WA, USA.
  • Mathias RA; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
  • Yanek LR; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
  • Heckbert SR; Channing Division of Network Medicine and Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Smith NL; Channing Division of Network Medicine and Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Wiggins KL; Channing Division of Network Medicine and Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Raffield LM; Channing Division of Network Medicine and Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Carson AP; National Heart, Lung and Blood Institute, Population Sciences Branch, Framingham, MA, USA.
  • Rotter JI; National Heart, Lung and Blood Institute, Population Sciences Branch, Framingham, MA, USA.
  • Rich SS; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Manichaikul AW; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Gu CC; Department of Epidemiology, University of Washington, Seattle, WA, USA.
  • Chen YI; Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Washington, Seattle, WA, USA.
  • Lee WJ; Department of Epidemiology, University of Washington, Seattle, WA, USA.
  • Shoemaker MB; Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Washington, Seattle, WA, USA.
  • Roden DM; Seattle Epidemiologic Research and Information Center, Department of Veterans Affairs Office of Research and Development, Seattle, WA, USA.
  • Kooperberg C; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
  • Auer PL; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Desai P; Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
  • Blackwell TW; 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.
  • Smith AV; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
  • Reiner AP; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
  • Jaiswal S; Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA.
  • Weinstock JS; Medical Genetics Translational Genomics and Population Sciences (TGPS), Lundquist Institute for Biomedical Innovation, Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Bick AG; Department of Medical Research, Taichung Veterans General Hospital, Taichung City, Taiwan.
Nat Aging ; 4(8): 1043-1052, 2024 Aug.
Article em En | MEDLINE | ID: mdl-38834882
ABSTRACT
Clonal hematopoiesis of indeterminate potential (CHIP), whereby somatic mutations in hematopoietic stem cells confer a selective advantage and drive clonal expansion, not only correlates with age but also confers increased risk of morbidity and mortality. Here, we leverage genetically predicted traits to identify factors that determine CHIP clonal expansion rate. We used the passenger-approximated clonal expansion rate method to quantify the clonal expansion rate for 4,370 individuals in the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) cohort and calculated polygenic risk scores for DNA methylation aging, inflammation-related measures and circulating protein levels. Clonal expansion rate was significantly associated with both genetically predicted and measured epigenetic clocks. No associations were identified with inflammation-related lab values or diseases and CHIP expansion rate overall. A proteome-wide search identified predicted circulating levels of myeloid zinc finger 1 and anti-Müllerian hormone as associated with an increased CHIP clonal expansion rate and tissue inhibitor of metalloproteinase 1 and glycine N-methyltransferase as associated with decreased CHIP clonal expansion rate. Together, our findings identify epigenetic and proteomic patterns associated with the rate of hematopoietic clonal expansion.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteômica / Epigênese Genética / Hematopoiese Clonal Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
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PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteômica / Epigênese Genética / Hematopoiese Clonal Idioma: En Ano de publicação: 2024 Tipo de documento: Article