Epigenetic entropy, socioeconomic differences, and health and lifespan in the Women's Health Initiative

Khyobeni Mozhui; Athena Starlard-Davenport; Yangbo Sun; Aladdin H Shadyab; Ramon Casanova; Fridtjof Thomas; Robert B Wallace; Jay H Fowke; Karen C Johnson

doi:10.1186/s13148-026-02180-3

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Epigenetic entropy, socioeconomic differences, and health and lifespan in the Women's Health Initiative

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Epigenetic entropy, socioeconomic differences, and health and lifespan in the Women's Health Initiative

Khyobeni Mozhui, Athena Starlard-Davenport, Yangbo Sun, Aladdin H Shadyab, Ramon Casanova, Fridtjof Thomas, Robert B Wallace, Jay H Fowke and Karen C Johnson

Clinical epigenetics

06/19/2026

DOI: 10.1186/s13148-026-02180-3

PMID: 42321810

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Abstract

Aging is marked by changes in DNA methylation (DNAm) including an increase in randomness or entropy in the epigenome. Here, we computed epigenetic entropy using DNAm data from the Women's Health Initiative (WHI) ancillary study AS315 (n = 2192), and tested for replication in WHI ancillary studies, BA23 (n = 1989) and AS311 (n = 868). We investigated how different metrics of epigenetic stochasticity relate to demographic variables, health, and mortality risk, and how these compare to machine-learning based models of aging such as the DunedinPACE. Epigenetic entropy had robust and consistent negative associations with income and education in the WHI. Notably, low income was related to increased stochasticity and higher methylation in DNA regions that are targeted by the polycomb proteins-key regulators of cellular memory and embryonic development. While higher income was associated with reduced entropy scores and lower DunedinPACE in White women, this effect of income was diminished in Black and Hispanic women, and on average, Black and Hispanic women had relatively higher stochastic variability. Painting a complex picture, our analysis of the polycomb regions in a small cohort of children showed significant positive associations with parental income. Additionally, in the WHI, higher DunedinPACE predicted higher mortality risk, while the maintenance of methylation at enhancer regions was associated with improved survival. These findings indicate close ties between social and economic factors and aspects of epigenetic aging, and highlight the polycomb targeted CpGs as potential sensors of the social environment and related exposures across demographic groups.

Aging

DNA methylation

Disparity

Polycomb complex

Epigenetic entropy

Socioeconomics

Details

Title: Subtitle: Epigenetic entropy, socioeconomic differences, and health and lifespan in the Women's Health Initiative
Creators: Khyobeni Mozhui - University of Tennessee Health Science Center
Athena Starlard-Davenport - University of Tennessee Health Science Center
Yangbo Sun - University of Tennessee Health Science Center
Aladdin H Shadyab - University of California San Diego
Ramon Casanova - Wake Forest University
Fridtjof Thomas - University of Tennessee Health Science Center
Robert B Wallace - University of Iowa
Jay H Fowke - University of Tennessee Health Science Center
Karen C Johnson - University of Tennessee Health Science Center
Resource Type: Journal article
Publication Details: Clinical epigenetics
DOI: 10.1186/s13148-026-02180-3
PMID: 42321810
NLM abbreviation: Clin Epigenetics
ISSN: 1868-7083
eISSN: 1868-7083
Publisher: Springer Nature
Language: English
Electronic publication date: 06/19/2026
Academic Unit: Epidemiology; Injury Prevention Research Center
Record Identifier: 9985175467302771

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