Characterizing epigenetic aging in an adult sickle cell disease cohort.

dc.contributor.author

Lê, Brandon M

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Hatch, Daniel

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Yang, Qing

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Shah, Nirmish

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Luyster, Faith S

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Garrett, Melanie E

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Tanabe, Paula

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Ashley-Koch, Allison E

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Knisely, Mitchell R

dc.date.accessioned

2024-02-01T17:17:01Z

dc.date.available

2024-02-01T17:17:01Z

dc.date.issued

2024-01

dc.description.abstract

Abstract

Sickle cell disease (SCD) affects ∼100 000 predominantly African American individuals in the United States, causing significant cellular damage, increased disease complications, and premature death. However, the contribution of epigenetic factors to SCD pathophysiology remains relatively unexplored. DNA methylation (DNAm), a primary epigenetic mechanism for regulating gene expression in response to the environment, is an important driver of normal cellular aging. Several DNAm epigenetic clocks have been developed to serve as a proxy for cellular aging. We calculated the epigenetic ages of 89 adults with SCD (mean age, 30.64 years; 60.64% female) using 5 published epigenetic clocks: Horvath, Hannum, PhenoAge, GrimAge, and DunedinPACE. We hypothesized that in chronic disease, such as SCD, individuals would demonstrate epigenetic age acceleration, but the results differed depending on the clock used. Recently developed clocks more consistently demonstrated acceleration (GrimAge, DunedinPACE). Additional demographic and clinical phenotypes were analyzed to explore their association with epigenetic age estimates. Chronological age was significantly correlated with epigenetic age in all clocks (Horvath, r = 0.88; Hannum, r = 0.89; PhenoAge, r = 0.85; GrimAge, r = 0.88; DunedinPACE, r = 0.34). The SCD genotype was associated with 2 clocks (PhenoAge, P = .02; DunedinPACE, P < .001). Genetic ancestry, biological sex, β-globin haplotypes, BCL11A rs11886868, and SCD severity were not associated. These findings, among the first to interrogate epigenetic aging in adults with SCD, demonstrate epigenetic age acceleration with recently developed epigenetic clocks but not older-generation clocks. Further development of epigenetic clocks may improve their predictive ability and utility for chronic diseases such as SCD.
dc.identifier

498752

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2473-9529

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2473-9537

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https://hdl.handle.net/10161/30065

dc.language

eng

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American Society of Hematology

dc.relation.ispartof

Blood advances

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10.1182/bloodadvances.2023011188

dc.rights.uri

https://creativecommons.org/licenses/by-nc/4.0

dc.subject

Humans

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Anemia, Sickle Cell

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Epigenesis, Genetic

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Aging

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Adult

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Female

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Male

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Cellular Senescence

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Black or African American

dc.title

Characterizing epigenetic aging in an adult sickle cell disease cohort.

dc.type

Journal article

duke.contributor.orcid

Yang, Qing|0000-0003-4844-4690

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Shah, Nirmish|0000-0002-7506-0935

duke.contributor.orcid

Ashley-Koch, Allison E|0000-0001-5409-9155

pubs.begin-page

47

pubs.end-page

55

pubs.issue

1

pubs.organisational-group

Duke

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Sanford School of Public Policy

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School of Medicine

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School of Nursing

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Basic Science Departments

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Clinical Science Departments

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Institutes and Centers

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Biostatistics & Bioinformatics

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Molecular Genetics and Microbiology

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Medicine

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Pediatrics

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Medicine, Hematology

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Medicine, Nephrology

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Pediatrics, Hematology-Oncology

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Institutes and Provost's Academic Units

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University Institutes and Centers

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Duke Institute for Brain Sciences

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Duke Molecular Physiology Institute

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Initiatives

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Center for Child and Family Policy

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Emergency Medicine

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Duke - Margolis Center For Health Policy

pubs.publication-status

Published

pubs.volume

8

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