Peer-Reviewed Publication
Nat Commun2026May 21, 2026Journal Article
Co-occurring clonal hematopoiesis exhibits strong selection and high leukemia risk.
Kara M Barnao1, Aubrey K Hubbard2, Irenaeus C C Chan3, Weiyin Zhou2,4, Yasminka A Jakubek5, Giulio Genovese6, Wendy S W Wong2, Rebecca L Kelly2, Corey D Young2, Derek W Brown2, Wen-Yi Huang2, Neal D Freedman2, Kristine Jones2,4, Amy Hutchinson2,4, Belynda Hicks2,4, Duc Tran3, Donna Arnett7, Kathleen C Barnes8, Joshua C Bis9, Eric Boerwinkle10, Jennifer A Brody9, April P Carson11, Daniel I Chasman12,13, Michael H Cho14, Pinkal Desai15, Margaret F Doyle16, Myriam Fornage10,17, Xiuqing Guo18, Nancy Heard-Costa19, Marguerite Ryan Irvin20, Andrew D Johnson21, Sharon L R Kardia22, Charles Kooperberg23, Daniel Levy21, Joshua P Lewis24, Yun Li25, Ruth J F Loos26,27, Taralynn M Mack28, Rasika A Mathias29, Braxton D Mitchell24, Kari E North30, Nathan Pankratz31, Patricia A Peyser22, Michael H Preuss26, Bruce M Psaty9,32,33, Laura M Raffield34, Susan Redline35, Stephen S Rich36, Jerome I Rotter37, Edwin K Silverman14, Albert V Smith38, Jennifer A Smith22,39, Adrienne Stilp40, Yin Cao41,42,43, Paul Scheet44, Alexander P Reiner45, Alexander G Bick28, Stephen J Chanock2, Paul L Auer46, Kelly L Bolton3, Mitchell J Machiela47
1Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA. kara.barnao@nih.gov.
2Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA.
3Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
4Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD, USA.
5Department of Internal Medicine, University of Kentucky, Lexington, KY, USA.
6Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
7University of South Carolina, Columbia, SC, USA.
8Galatea Bio, Inc., Miami, FL, USA.
9Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
10Department 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.
11Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
12Harvard Medical School, Boston, MA, USA.
13Division of Preventative Medicine, Brigham and Women's Hospital, Boston, MA, USA.
14Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
15Division of Hematology and Oncology, Weill Cornell Medical College, New York, NY, USA.
16Department of Pathology and Laboratory Medicine, The University of Vermont Lerner College of Medicine, Colchester, VT, USA.
17Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
18Department of Medicine, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
19Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
20Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
21Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
22Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
23Division of Public Health Science, Fred Hutchinson Cancer Center, Seattle, WA, USA.
24Department of Medicine, University of Maryland Baltimore, Baltimore, MD, USA.
25Department of Genetics, Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
26The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
27Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
28Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
29Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA.
30Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
31Depart of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
32Department of Medicine, University of Washington, Seattle, WA, USA.
33Department of Health Systems and Population Health, University of Washington, Seattle, WA, USA.
34Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
35Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.
36Department of Genome Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA.
37The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
38Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
39Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
40Department of Biostatistics, University of Washington, Seattle, WA, USA.
41Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
42Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.
43Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
44Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
45Department of Epidemiology, University of Washington, Seattle, WA, USA.
46Division of Biostatistics, Data Science Institute, and Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA.
47Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA. mitchell.machiela@nih.gov.
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…
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