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An epigenetic predictor of death captures multi-modal measures of brain health.

ABSTRACT: Individuals of the same chronological age exhibit disparate rates of biological ageing. Consequently, a number of methodologies have been proposed to determine biological age and primarily exploit variation at the level of DNA methylation (DNAm). A novel epigenetic clock, termed 'DNAm GrimAge' has outperformed its predecessors in predicting the risk of mortality as well as many age-related morbidities. However, the association between DNAm GrimAge and cognitive or neuroimaging phenotypes remains unknown. We explore these associations in the Lothian Birth Cohort 1936 (n = 709, mean age 73 years). Higher DNAm GrimAge was strongly associated with all-cause mortality over the eighth decade (Hazard Ratio per standard deviation increase in GrimAge: 1.81, P < 2.0 × 10^-16). Higher DNAm GrimAge was associated with lower age 11 IQ (β = -0.11), lower age 73 general cognitive ability (β = -0.18), decreased brain volume (β = -0.25) and increased brain white matter hyperintensities (β = 0.17). There was tentative evidence for a longitudinal association between DNAm GrimAge and cognitive decline from age 70 to 79. Sixty-nine of 137 health- and brain-related phenotypes tested were significantly associated with GrimAge. Adjusting all models for childhood intelligence attenuated to non-significance a small number of associations (12/69 associations; 6 of which were cognitive traits), but not the association with general cognitive ability (33.9% attenuation). Higher DNAm GrimAge associates with lower cognitive ability and brain vascular lesions in older age, independently of early-life cognitive ability. This epigenetic predictor of mortality associates with different measures of brain health and may aid in the prediction of age-related cognitive decline.

SUBMITTER: Hillary RF

PROVIDER: S-EPMC8550950 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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An epigenetic predictor of death captures multi-modal measures of brain health.

Hillary Robert F RF Stevenson Anna J AJ Cox Simon R SR McCartney Daniel L DL Harris Sarah E SE Seeboth Anne A Higham Jon J Sproul Duncan D Taylor Adele M AM Redmond Paul P Corley Janie J Pattie Alison A Hernández Maria Del C Valdés MDCV Muñoz-Maniega Susana S Bastin Mark E ME Wardlaw Joanna M JM Horvath Steve S Ritchie Craig W CW Spires-Jones Tara L TL McIntosh Andrew M AM Evans Kathryn L KL Deary Ian J IJ Marioni Riccardo E RE

Molecular psychiatry 20191203 8

Individuals of the same chronological age exhibit disparate rates of biological ageing. Consequently, a number of methodologies have been proposed to determine biological age and primarily exploit variation at the level of DNA methylation (DNAm). A novel epigenetic clock, termed 'DNAm GrimAge' has outperformed its predecessors in predicting the risk of mortality as well as many age-related morbidities. However, the association between DNAm GrimAge and cognitive or neuroimaging phenotypes remains ...[more]

PMID: 31796892

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An epigenetic predictor of death captures multi-modal measures of brain health.

Publications

An epigenetic predictor of death captures multi-modal measures of brain health.

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