Clonal hematopoiesis of indeterminate potential, DNA methylation, and risk for coronary artery disease.

Clonal Hematopoiesis / genetics Coronary Artery Disease / genetics DNA Methylation / genetics Hematopoiesis / genetics Hematopoietic Stem Cells Humans

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
12 09 2022
Historique:
received: 17 03 2022
accepted: 01 09 2022
entrez: 12 9 2022
pubmed: 13 9 2022
medline: 15 9 2022
Statut: epublish

Résumé

Age-related changes to the genome-wide DNA methylation (DNAm) pattern observed in blood are well-documented. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by the age-related acquisition and expansion of leukemogenic mutations in hematopoietic stem cells (HSCs), is associated with blood cancer and coronary artery disease (CAD). Epigenetic regulators DNMT3A and TET2 are the two most frequently mutated CHIP genes. Here, we present results from an epigenome-wide association study for CHIP in 582 Cardiovascular Health Study (CHS) participants, with replication in 2655 Atherosclerosis Risk in Communities (ARIC) Study participants. We show that DNMT3A and TET2 CHIP have distinct and directionally opposing genome-wide DNAm association patterns consistent with their regulatory roles, albeit both promoting self-renewal of HSCs. Mendelian randomization analyses indicate that a subset of DNAm alterations associated with these two leading CHIP genes may promote the risk for CAD.

Identifiants

DOI: 10.1038/s41467-022-33093-3 PMID: 36097025 PMC: PMC9468335
pubmed: 36097025
doi: 10.1038/s41467-022-33093-3
pii: 10.1038/s41467-022-33093-3
pmc: PMC9468335
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, American Recovery and Reinvestment Act Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

5350

Subventions

Organisme : NHLBI NIH HHS
ID : R01 HL142711
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL086694
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL146860
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL105756
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201700002I
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201700005I
Pays : United States
Organisme : NIH HHS
ID : DP5 OD029586
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL127564
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268200800007C
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL135242
Pays : United States
Organisme : NHLBI NIH HHS
ID : RC2 HL102926
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85080
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000124
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL141989
Pays : United States
Organisme : NHLBI NIH HHS
ID : RC2 HL102925
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG023629
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201800001C
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL080295
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001881
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL148565
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL120393
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201200036C
Pays : United States
Organisme : NHLBI NIH HHS
ID : RC2 HL102419
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS087541
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL103612
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL116640
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201700001I
Pays : United States
Organisme : NHLBI NIH HHS
ID : RC2 HL103010
Pays : United States
Organisme : NHLBI NIH HHS
ID : 75N92021D00006
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL092111
Pays : United States
Organisme : NHGRI NIH HHS
ID : T32 HG000040
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201700004I
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL148050
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85082
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR041398
Pays : United States
Organisme : NHLBI NIH HHS
ID : DP2 HL157540
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC55222
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL111089
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85079
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG059727
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85083
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL151152
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85086
Pays : United States
Organisme : NIA NIH HHS
ID : U34 AG051418
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK125782
Pays : United States
Organisme : NHGRI NIH HHS
ID : U54 HG003273
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201700003I
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL130114
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL087652
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL151283
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL116747
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85081
Pays : United States
Organisme : NIA NIH HHS
ID : T32 AG047126
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES009089
Pays : United States

Informations de copyright

© 2022. The Author(s).

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Auteurs

M D Mesbah Uddin (MDM)

Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, 02114, USA.
ORCID: 0000-0003-1846-0411

Ngoc Quynh H Nguyen (NQH)

Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.

Bing Yu (B)

Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.

Jennifer A Brody (JA)

Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, 98101, USA.
ORCID: 0000-0001-8509-148X

Akhil Pampana (A)

Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
ORCID: 0000-0002-4167-0540

Tetsushi Nakao (T)

Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, 02114, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02115, USA.
Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA.
ORCID: 0000-0001-9979-2682

Myriam Fornage (M)

Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
ORCID: 0000-0003-0677-8158

Jan Bressler (J)

Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
ORCID: 0000-0001-6578-4772

Nona Sotoodehnia (N)

Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, 98101, USA.

Joshua S Weinstock (JS)

Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, 48109, USA.
ORCID: 0000-0001-7013-1899

Michael C Honigberg (MC)

Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, 02114, USA.
ORCID: 0000-0001-8630-5021

Daniel Nachun (D)

Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
ORCID: 0000-0002-0271-1135

Romit Bhattacharya (R)

Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, 02114, USA.
Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA.

Gabriel K Griffin (GK)

Department of Pathology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Department of Pathology, Brigham and Women's Hospital, Boston, MA, 02115, USA.
Epigenomics Program, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.

Varuna Chander (V)

Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA.
Department of Genetics and Genomics, Baylor College of Medicine, Houston, TX, 77030, USA.

Richard A Gibbs (RA)

Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA.
Department of Genetics and Genomics, Baylor College of Medicine, Houston, TX, 77030, USA.

Jerome I Rotter (JI)

The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.

Chunyu Liu (C)

Department of Biostatistics, School of Public Health, Boston University, Boston, MA, 02118, USA.
Framingham Heart Study, Boston University and NHLBI/NIH, Framingham, MA, 01702, USA.

Andrea A Baccarelli (AA)

Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, 10032, USA.
ORCID: 0000-0002-3436-0640

Daniel I Chasman (DI)

Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA.
Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, 02215, USA.
ORCID: 0000-0003-3357-0862

Eric A Whitsel (EA)

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, 27516, USA.
Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC, 27516, USA.
ORCID: 0000-0003-4843-3641

Douglas P Kiel (DP)

Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA.
Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, 02131, USA.
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA.
Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
ORCID: 0000-0001-8474-0310

Joanne M Murabito (JM)

Framingham Heart Study, Boston University and NHLBI/NIH, Framingham, MA, 01702, USA.
Department of Medicine, Section of General Internal Medicine, Boston University School of Medicine and Boston Medical Center, Boston, MA, 02118, USA.

Eric Boerwinkle (E)

Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA.

Benjamin L Ebert (BL)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02115, USA.
Howard Hughes Medical Institute, Boston, MA, 20815, USA.
ORCID: 0000-0003-0197-5451

Siddhartha Jaiswal (S)

Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
ORCID: 0000-0002-9597-0477

James S Floyd (JS)

Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, 98101, USA.
Department of Epidemiology, University of Washington, Seattle, WA, 98101, USA.

Alexander G Bick (AG)

Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
ORCID: 0000-0001-5824-9595

Christie M Ballantyne (CM)

Department of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA.
ORCID: 0000-0002-6432-1730

Bruce M Psaty (BM)

Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, 98101, USA.
Department of Epidemiology, University of Washington, Seattle, WA, 98101, USA.
Department of Health Systems and Population Health, University of Washington, Seattle, WA, 98101, USA.
ORCID: 0000-0002-7278-2190

Pradeep Natarajan (P)

Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA. pnatarajan@mgh.harvard.edu.
Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, 02114, USA. pnatarajan@mgh.harvard.edu.
Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA. pnatarajan@mgh.harvard.edu.
ORCID: 0000-0001-8402-7435

Karen N Conneely (KN)

Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, 30322, USA. kconnee@emory.edu.
ORCID: 0000-0002-1994-6934

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Classifications MeSH

questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiogiques du sang › Hématopoïèse › Hématopoïèse clonale › Clonal hematopoiesis of indeterminate...
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Ischémie myocardique › Maladie coronarienne › Maladie des artères coronaires › Clonal hematopoiesis of indeterminate...
questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › Clonal hematopoiesis of indeterminate...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiogiques du sang › Hématopoïèse › Clonal hematopoiesis of indeterminate...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système hématopoïétique › Cellules de la moelle osseuse › Cellules souches hématopoïétiques › Clonal hematopoiesis of indeterminate...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Clonal hematopoiesis of indeterminate...