Projects per year
Abstract / Description of output
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.
Original language | English |
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Pages (from-to) | 1-11 |
Number of pages | 11 |
Journal | Molecular Psychiatry |
Volume | N/A |
DOIs | |
Publication status | Published - 3 Dec 2019 |
Fingerprint
Dive into the research topics of 'An epigenetic predictor of death captures multi-modal measures of brain health'. Together they form a unique fingerprint.Projects
- 7 Finished
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Brain imaging and cognitive ageing in the Lothian Birth Cohort 1936: III
Wardlaw, J., Bastin, M. & Deary, I.
1/05/15 → 30/04/19
Project: Research
Research output
- 1 Doctoral Thesis
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A multi–omics approach to understand the role of plasma proteins in cognitive ageing and dementia
Hillary, R., 2021Research output: Thesis › Doctoral Thesis
Profiles
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Riccardo Marioni
- Deanery of Molecular, Genetic and Population Health Sciences - Personal Chair of Molecular Epidemiology of Ageing
- Centre for Genomic and Experimental Medicine
- Edinburgh Neuroscience
Person: Academic: Research Active