학술논문
An epigenetic predictor of death captures multi-modal measures of brain health
Document Type
Article
Author
Hillary, Robert F.; Stevenson, Anna J.; Cox, Simon R.; McCartney, Daniel L.; Harris, Sarah E.; Seeboth, Anne; Higham, Jon; Sproul, Duncan; Taylor, Adele M.; Redmond, Paul; Corley, Janie; Pattie, Alison; Hernández, Maria del. C. Valdés; Muñoz-Maniega, Susana; Bastin, Mark E.; Wardlaw, Joanna M.; Horvath, Steve; Ritchie, Craig W.; Spires-Jones, Tara L.; McIntosh, Andrew M.; Evans, Kathryn L.; Deary, Ian J.; Marioni, Riccardo E.
Source
Molecular Psychiatry; August 2021, Vol. 26 Issue: 8 p3806-3816, 11p
Subject
Language
ISSN
13594184; 14765578
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.