Nature Communications

Co-occurring clonal hematopoiesis exhibits strong selection and high leukemia risk

K Kara M. Barnao A Aubrey K. Hubbard I Irenaeus C. C. Chan W Weiyin Zhou Y Yasminka A. Jakubek G Giulio Genovese W Wendy S. W. Wong R Rebecca L. Kelly C Corey D. Young D Derek W. Brown W Wen-Yi Huang N Neal D. Freedman (Division of Cancer Control and Population Sciences National Cancer Institute Rockville Maryland USA) K Kristine Jones A Amy Hutchinson B Belynda Hicks D Duc Tran (Institute of Physics, Johannes Gutenberg-University Mainz, Mainz, Germany.) D Donna Arnett K Kathleen C. Barnes J Joshua C. Bis E Eric Boerwinkle J Jennifer A. Brody A April P. Carson D Daniel I. Chasman M Michael H. Cho (Channing Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.) P Pinkal Desai M Margaret F. Doyle M Myriam Fornage X Xiuqing Guo N Nancy Heard-Costa (Chobanian & Avedisian School of Medicine, Boston University, Boston, MA, USA.) M Marguerite Ryan Irvin A Andrew D. Johnson S Sharon L. R. Kardia C Charles Kooperberg (Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.) D Daniel Levy (Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.) J Joshua P. Lewis Y Yun Li R Ruth J. F. Loos T Taralynn M. Mack R Rasika A. Mathias B Braxton D. Mitchell K Kari E. North N Nathan Pankratz P Patricia A. Peyser M Michael H. Preuss B Bruce M. Psaty L Laura M. Raffield (Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.) S Susan Redline S Stephen S. Rich (Department of Genome Sciences, School of Medicine, University of Virginia, Charlottesville, VA, USA.) J Jerome I. Rotter E Edwin K. Silverman (Channing Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.) A Albert V. Smith (Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA.) J Jennifer A. Smith A Adrienne Stilp Y Yin Cao P Paul Scheet A Alexander P. Reiner A Alexander G. Bick S Stephen J. Chanock P Paul L. Auer K Kelly L. Bolton M Mitchell J. Machiela

Abstract

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.

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Article Details

Volume / Issue Vol. 17, Issue 1
Published May 21, 2026
ISSN 2041-1723
Publisher Nature Portfolio

Journal Info

Nature Communications

Nature Portfolio
ISSN: 2041-1723 Open Access Life Sciences

Authors (61)

K

Kara M. Barnao

A

Aubrey K. Hubbard

I

Irenaeus C. C. Chan

W

Weiyin Zhou

Y

Yasminka A. Jakubek

G

Giulio Genovese

W

Wendy S. W. Wong

R

Rebecca L. Kelly

C

Corey D. Young

D

Derek W. Brown

W

Wen-Yi Huang

N

Neal D. Freedman

Division of Cancer Control and Population Sciences National Cancer Institute Rockville Maryland USA

K

Kristine Jones

A

Amy Hutchinson

B

Belynda Hicks

D

Duc Tran

Institute of Physics, Johannes Gutenberg-University Mainz, Mainz, Germany.

D

Donna Arnett

K

Kathleen C. Barnes

J

Joshua C. Bis

E

Eric Boerwinkle

J

Jennifer A. Brody

A

April P. Carson

D

Daniel I. Chasman

M

Michael H. Cho

Channing Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.

P

Pinkal Desai

M

Margaret F. Doyle

M

Myriam Fornage

X

Xiuqing Guo

N

Nancy Heard-Costa

Chobanian & Avedisian School of Medicine, Boston University, Boston, MA, USA.

M

Marguerite Ryan Irvin

A

Andrew D. Johnson

S

Sharon L. R. Kardia

C

Charles Kooperberg

Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.

D

Daniel Levy

Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.

J

Joshua P. Lewis

Y

Yun Li

R

Ruth J. F. Loos

T

Taralynn M. Mack

R

Rasika A. Mathias

B

Braxton D. Mitchell

K

Kari E. North

N

Nathan Pankratz

P

Patricia A. Peyser

M

Michael H. Preuss

B

Bruce M. Psaty

L

Laura M. Raffield

Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

S

Susan Redline

S

Stephen S. Rich

Department of Genome Sciences, School of Medicine, University of Virginia, Charlottesville, VA, USA.

J

Jerome I. Rotter

E

Edwin K. Silverman

Channing Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.

A

Albert V. Smith

Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA.

J

Jennifer A. Smith

A

Adrienne Stilp

Y

Yin Cao

P

Paul Scheet

A

Alexander P. Reiner

A

Alexander G. Bick

S

Stephen J. Chanock

P

Paul L. Auer

K

Kelly L. Bolton

M

Mitchell J. Machiela

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