TY - JOUR
T1 - An epigenetic predictor of death captures multi-modal measures of brain health
AU - Hillary, Robert
AU - Stevenson, Anna J.
AU - Cox, Simon R.
AU - McCartney, Daniel L.
AU - Harris, Sarah E.
AU - Seeboth, Anne
AU - Higham, Jonathan
AU - Sproul, Duncan
AU - Taylor, Adele
AU - Redmond, Paul
AU - Corley, Janie
AU - Pattie, Alison
AU - del C. Valdés Hernández, Maria
AU - Muñoz-Maniega, Susana
AU - Bastin, Mark E.
AU - Wardlaw, Joanna M.
AU - Horvath, Steve
AU - Ritchie, Craig W.
AU - Spires-Jones, Tara L.
AU - McIntosh, Andrew M.
AU - Evans, Kathryn L.
AU - Deary, Ian J.
AU - Marioni, Riccardo E.
PY - 2019/12/3
Y1 - 2019/12/3
N2 - 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.
AB - 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.
U2 - 10.1038/s41380-019-0616-9
DO - 10.1038/s41380-019-0616-9
M3 - Article
SN - 1359-4184
VL - N/A
SP - 1
EP - 11
JO - Molecular Psychiatry
JF - Molecular Psychiatry
ER -