ArticleNature communications2026
Co-occurring clonal hematopoiesis exhibits strong selection and high leukemia risk.
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In one paragraph
Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1citing papers in PubMed
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Who cites it
1 citing paper in PubMed.
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Authors and funding
61 authors.
Kara M BarnaoDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA. kara.barnao@nih.gov.ORCID http://orcid.org/0009-0006-2308-4464
Aubrey K HubbardDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA.ORCID http://orcid.org/0000-0003-4052-1110
Irenaeus C C ChanDivision of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0009-0004-3250-9626
Weiyin ZhouDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA.ORCID http://orcid.org/0000-0002-0467-3064
Yasminka A JakubekDepartment of Internal Medicine, University of Kentucky, Lexington, KY, USA.ORCID http://orcid.org/0000-0003-1427-1015
Giulio GenoveseProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-3066-5575
Wendy S W WongDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA.ORCID http://orcid.org/0000-0001-9850-3797
Rebecca L KellyDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA.ORCID http://orcid.org/0009-0009-4378-737X
Corey D YoungDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA.ORCID http://orcid.org/0000-0003-1841-3527
Derek W BrownDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA.ORCID http://orcid.org/0000-0001-8393-1713
Wen-Yi HuangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA.ORCID http://orcid.org/0000-0002-4440-3368
Neal D FreedmanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA.
Kristine JonesDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA.ORCID http://orcid.org/0000-0003-1584-8920
Amy HutchinsonDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA.
Belynda HicksDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA.ORCID http://orcid.org/0000-0001-8014-4888
Duc TranDivision of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0003-2918-8601
Donna ArnettUniversity of South Carolina, Columbia, SC, USA.
Kathleen C BarnesGalatea Bio, Inc., Miami, FL, USA.
Joshua C BisCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-3409-1110
Eric BoerwinkleDepartment of Epidemiology, Human Genetics, and Environmental Sciences, Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Jennifer A BrodyCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0001-8509-148X
April P CarsonDepartment of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.ORCID http://orcid.org/0000-0002-7970-6756
Daniel I ChasmanHarvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-3357-0862
Michael H ChoChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Pinkal DesaiDivision of Hematology and Oncology, Weill Cornell Medical College, New York, NY, USA.
Margaret F DoyleDepartment of Pathology and Laboratory Medicine, The University of Vermont Lerner College of Medicine, Colchester, VT, USA.ORCID http://orcid.org/0000-0001-6769-5386
Myriam FornageDepartment of Epidemiology, Human Genetics, and Environmental Sciences, Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID http://orcid.org/0000-0003-0677-8158
Xiuqing GuoDepartment of Medicine, 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 Heard-CostaDepartment of Medicine, Boston University School of Medicine, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9730-0306
Marguerite Ryan IrvinDepartment of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
Andrew D JohnsonPopulation Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-6369-5178
Sharon L R KardiaDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Charles KooperbergDivision of Public Health Science, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-7986-8560
Daniel LevyPopulation Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Joshua P LewisDepartment of Medicine, University of Maryland Baltimore, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-4107-6066
Yun LiDepartment of Genetics, Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-9275-4189
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/0000-0002-8532-5087
Taralynn M MackDivision of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Rasika A MathiasLaboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA.
Braxton D MitchellDepartment of Medicine, University of Maryland Baltimore, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-4920-4744
Kari E NorthDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Nathan PankratzDepart of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.ORCID http://orcid.org/0000-0001-5958-693X
Patricia A PeyserDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-9717-8459
Michael H PreussThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0001-5266-8465
Bruce M PsatyCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-7278-2190
Laura M RaffieldDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Susan RedlineDivision of Sleep Medicine, Harvard Medical School, Boston, MA, USA.
Stephen S RichDepartment of Genome Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0003-3872-7793
Jerome I RotterThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.ORCID http://orcid.org/0000-0001-7191-1723
Edwin K SilvermanChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Albert V SmithDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0003-1942-5845
Jennifer A SmithDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-3575-5468
Adrienne StilpDepartment of Biostatistics, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-3910-0776
Yin CaoDivision of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-9835-7662
Paul ScheetDepartment of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-5173-7497
Alexander P ReinerDepartment of Epidemiology, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-1427-4470
Alexander G BickDivision of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0001-5824-9595
Stephen J ChanockDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA.ORCID http://orcid.org/0000-0002-2324-3393
Paul L AuerDivision of Biostatistics, Data Science Institute, and Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA.ORCID http://orcid.org/0000-0003-1735-8044
Kelly L BoltonDivision of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-6584-3357
Mitchell J MachielaDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA. mitchell.machiela@nih.gov.ORCID http://orcid.org/0000-0001-6538-9705
Funding
Next generation functional genomics of hematology traitsR01HL146500 · NHLBI · UNIVERSITY OF WASHINGTON · PI ALEXANDER P REINER · 2020 to 2026
$5.7MStructural Variation and Hematological TraitsR01HL165061 · NHLBI · UNIVERSITY OF WASHINGTON · PI NATHAN D PANKRATZ, ALEXANDER P REINER · 2023 to 2026
$3.1MInfrastructure for mentored access to CHS data and specimensR01HL172803 · NHLBI · UNIVERSITY OF WASHINGTON · PI James S Floyd, Michelle Christina Odden · 2025 to 2026
$2.7MNHLBI NIH HHS R01 HL146500NHLBI NIH HHS R01 HL165061NHLBI NIH HHS R01 HL172803
Abstract
Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are two types of clonal hematopoiesis (CH) associated with hematological parameters and malignancy risk. Here we show, in genomic data from 546,090 biobank participants, that co-occurring CH (≥2 CH mutations detected) is present in 1.6% of cancer-free individuals and shows strong evidence for selection (up to 804x enrichment). Co-occurrence is more frequent in those with a prior cancer (3.6%), suggesting treatment-induced selection. Acquisition of CHIP usually precedes mCAs with co-occurrences manifesting stronger phenotypic disruptions in telomere attrition and hematologic parameters than component CH events. Individuals with co-occurring CH have pronounced elevations in risk of myeloid and lymphoid malignancies (HRs>40), particularly when CHIP and mCAs overlap genomically. Our findings indicate CH co-occurrences are selected for in the aging population and identify CH clones with notable implications for future malignancy risk.
Indexed as
Clonal HematopoiesisLeukemiaChromosome AberrationsHumansMutation
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