ArticleNature communications2024
Determinants of mosaic chromosomal alteration fitness.
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Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7citing papers in PubMed
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Who cites it
7 citing papers in PubMed.
- Longitudinal characterization of mosaic chromosomal alterations identifies factors influencing clonal dynamics of leukocytes.Nature communications · 2026Article
- Hematopoietic mosaic chromosomal alterations are pleiotropic drivers of inflammaging, multimorbidity, and mortality.medRxiv : the preprint server for health sciences · 2026Article
- Patterns and drivers of 43,617 mosaic chromosomal alterations in blood.Nature genetics · 2026Article
- Clonal Hematopoiesis in Cancer and Cardiovascular Disease: JACC: CardioOncology State-of-the-Art Review.JACC. CardioOncology · 2025Review
- Deleterious mitochondrial heteroplasmies exhibit increased longitudinal change in variant allele fraction.iScience · 2025Article
- Clonal hematopoiesis: elements associated with clonal expansion and diseases.Blood research · 2025Review
- Genetic drivers and clinical consequences of mosaic chromosomal alterations in 1 million individuals.medRxiv : the preprint server for health sciences · 2025Article
Corrections and comments
- Update of
Authors and funding
44 authors.
Yash Pershad *Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-2282-1403
Taralynn Mack *Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, USA.
Hannah PoisnerVanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, USA.ORCID http://orcid.org/0000-0003-1652-3642
Yasminka A JakubekInternal Medicine, Biomedical Informatics, University of Kentucky, Lexington, KY, USA.
Adrienne M StilpBiostatistics, School of Public Health, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-3910-0776
Braxton D MitchellDept of Medicine, Endocrinology, Diabetes, and Nutrition, University of Maryland, Baltimore, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-4920-4744
Joshua P LewisDept of Medicine, Endocrinology, Diabetes, and Nutrition, University of Maryland, Baltimore, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-4107-6066
Eric BoerwinkleHuman 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.
Ruth J F LoosThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0001-8312-1438
Nathalie ChamiThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-8547-6424
Zhe WangThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-8046-4969
Kathleen BarnesDivision of Biomedical Informatics & Personalized Medicine, University of Colorado Anschutz, Aurora, CO, USA.ORCID http://orcid.org/0000-0002-3030-4705
Nathan PankratzDepartment of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN, USA.ORCID http://orcid.org/0000-0001-5958-693X
Myriam FornageHuman 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.ORCID http://orcid.org/0000-0003-0677-8158
Susan RedlineDivision of Sleep Medicine, Harvard Medical School, Boston, MA, USA.
Bruce M PsatyCardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Systems and Population Health, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-7278-2190
Joshua C BisCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-3409-1110
Ali ShojaieBiostatistics, University of Washington, Seattle, WA, USA.
Edwin K SilvermanChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Michael H ChoChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Jeong H YunChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-4361-8295
Dawn DeMeoChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Daniel LevyNational Heart, Lung and Blood Institute, Population Sciences Branch, Framingham, MA, USA.
Andrew D JohnsonNational Heart, Lung and Blood Institute, Population Sciences Branch, Framingham, MA, USA.ORCID http://orcid.org/0000-0001-6369-5178
Rasika A MathiasDivision of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MA, USA.ORCID http://orcid.org/0000-0002-2282-9042
Margaret A TaubDepartment of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MA, USA.
Donna ArnettDepartment of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Kari E NorthDepartment of Epidemiology, University of North Carolina Chapel-Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-8903-0366
Laura M RaffieldDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-7892-193X
April P CarsonDepartment of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.ORCID http://orcid.org/0000-0002-7970-6756
Margaret F DoyleDepartment of Pathology & Laboratory Medicine, The University of Vermont Larner College of Medicine, Colchester, VT, USA.
Stephen S RichCenter for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0003-3872-7793
Jerome I RotterPediatrics, Genomic Outcomes, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.ORCID http://orcid.org/0000-0001-7191-1723
Xiuqing GuoPediatrics, Genomic Outcomes, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.ORCID http://orcid.org/0000-0002-5264-5068
Nancy J CoxDivision of Genetic Medicine, Department of Medicine, Vanderbilt University and Vanderbilt University Medical Center, Nashville, TN, USA.
Dan M RodenDepartments of Medicine, Pharmacology, and Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-6302-0389
Nora FranceschiniDepartment of Epidemiology, University of North Carolina Chapel-Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0009-0001-8346-3662
Pinkal DesaiWeill Cornell Medical College, New York, NY, USA.
Alex P ReinerPublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-1427-4470
Paul L AuerDivision of Biostatistics, Insitute for Health & Equity and Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA.ORCID http://orcid.org/0000-0003-1735-8044
Paul A ScheetDept of Epidemiology, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-5173-7497
Siddhartha JaiswalDepartment of Pathology, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-9597-0477
Joshua S WeinstockCenter for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0001-7013-1899
Alexander G BickDivision of Genetic Medicine, Department of Medicine, Vanderbilt University and Vanderbilt University Medical Center, Nashville, TN, USA. alexander.bick@vumc.org.ORCID http://orcid.org/0000-0001-5824-9595
Funding
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007347 · NIGMS · VANDERBILT UNIVERSITY · PI WILLIAMS, CHRISTOPHER S. · 1985 to 2023
$26.3MStudies of Rare Genetic Variation in the Isolated Population of SardiniaR01HL117626 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABECASIS, GONCALO · 2013 to 2016
$10.5MCHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5MRare variants and NHLBI traits in deeply phenotyped cohortsR01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2014 to 2016
$8.9MRare variants and NHLBI traits in deeply phenotyped cohortsU01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2017 to 2018
$5.6MMedical Scientist Training ProgramT32GM152284 · NIGMS · VANDERBILT UNIVERSITY · PI Christopher S. Williams · 2024 to 2026
$4.8MLeveraging ancestry to map kidney lociR01MD012765 · NIMHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FRANCESCHINI, NORA · 2017 to 2021
$3.6MEstablishing the dynamics of lymphoid clonal hematopoiesis and its aging-related disease consequencesR01AG083736 · NIA · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Paul L. Auer, Alexander Bick · 2023 to 2026
$2.8MGenetics of kidney disease in diverse populationsR01DK117445 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FRANCESCHINI, NORA · 2018 to 2022
$2.7MTargeting Clonal Hematopoiesis of Indeterminate Potential Using Human GeneticsDP5OD029586 · OD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BICK, ALEXANDER · 2020 to 2024
$2.3MAdmixture mapping of mosaic copy number alterations for identification of cancer driversK22CA258678 · NCI · UNIVERSITY OF KENTUCKY · PI JAKUBEK SWARTZLANDER, YASMINKA ALEKSANDRA · 2022 to 2024
$541kNCI NIH HHS K22 CA258678NHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS R01 HL117626NHLBI NIH HHS R01 HL120393NHLBI NIH HHS U01 HL120393NIA NIH HHS R01 AG083736NIDDK NIH HHS R01 DK117445NIGMS NIH HHS T32 GM007347NIGMS NIH HHS T32 GM152284NIH HHS DP5 OD029586NIMHD NIH HHS R01 MD012765
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 (R
Indexed as
Chromosome AberrationsClonal HematopoiesisMosaicismAgedCross-Sectional StudiesFemaleGenome-Wide Association StudyHematopoietic Stem CellsHumansJanus Kinase 2Loss of HeterozygosityMaleMiddle AgedMutationPolymorphism, Single NucleotideTelomeraseJAK2 protein, humanJanus Kinase 2TelomeraseTERT protein, human
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