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Sample Preparation to Bioinformatics Analysis of DNA Methylation: Association Strategy for Obesity and Related Trait Studies
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DNA Methylation Signatures of Atherosclerosis and Vascular-Related Outcomes in U.S. and Irish Population-Based

Farah Ammous, Trey Smith, Siobhan Scarlett

    Medrxiv : the Preprint Server for Health Sciences
    |June 5, 2026
    PubMed

    Insights

    DNA methylation (DNAm) scores for atherosclerosis, like DNAm-CAC and DNAm-cPlaque, are linked to cardiovascular, cognitive, and kidney health in older adults. These scores may reflect systemic vascular aging processes impacting multiple health outcomes.

    Area of Science:

    • Epigenetics and Aging
    • Cardiovascular Disease Epidemiology
    • Gerontology

    Background:

    • Atherosclerosis is a systemic vascular disease impacting cardiovascular, cognitive, and renal health.
    • DNA methylation (DNAm)-based scores may quantify cumulative biological processes of vascular aging.
    • Subclinical atherosclerosis assessment is crucial for understanding age-related disease trajectories.

    Purpose of the Study:

    • To investigate the association of DNAm scores for coronary artery calcification (DNAm-CAC) and carotid plaque (DNAm-cPlaque) with prevalent and incident health outcomes.
    • To examine these associations in two large, population-based cohorts of older adults: the Health and Retirement Study (HRS) and The Irish Longitudinal Study on Ageing (TILDA).
    • To explore the role of DNAm scores in capturing systemic vascular processes related to aging.

    Main Methods:

    • Utilized DNAm scores derived from imaging-based subclinical atherosclerosis data.
    • Analyzed associations with cardiovascular disease, cognitive function, and estimated glomerular filtration rate (eGFR) in HRS and TILDA cohorts.
    • Employed multivariable regression models, adjusting for demographic, clinical, and socioeconomic factors.

    Main Results:

    • Higher DNAm scores were associated with adverse cardiometabolic profiles and socioeconomic indicators.
    • In HRS, DNAm-CAC correlated with prevalent cardiovascular disease, lower cognitive function, and lower eGFR.
    • In both cohorts, DNAm scores were linked to poorer cognitive function and, in TILDA, increased risk of incident cardiovascular disease and lower eGFR, with associations attenuated by socioeconomic factors.

    Conclusions:

    • DNAm-based atherosclerosis scores appear to capture systemic vascular processes impacting multiple age-related outcomes.
    • These scores reflect cumulative vascular aging and are associated with cardiovascular, cognitive, and renal health.
    • Further research is needed to elucidate the biological pathways and the influence of social determinants on these associations.

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