Characterisation of an inflammation-related epigenetic score and its association with cognitive ability.

Abstract:

BACKGROUND:Chronic systemic inflammation has been associated with incident dementia, but its association with age-related cognitive decline is less clear. The acute responses of many inflammatory biomarkers mean they may provide an unreliable picture of the chronicity of inflammation. Recently, a large-scale epigenome-wide association study identified DNA methylation correlates of C-reactive protein (CRP)-a widely used acute-phase inflammatory biomarker. DNA methylation is thought to be relatively stable in the short term, marking it as a potentially useful signature of exposure. METHODS:We utilise a DNA methylation-based score for CRP and investigate its trajectories with age, and associations with cognitive ability in comparison with serum CRP and a genetic CRP score in a longitudinal study of older adults (n = 889) and a large, cross-sectional cohort (n = 7028). RESULTS:We identified no homogeneous trajectories of serum CRP with age across the cohorts, whereas the epigenetic CRP score was consistently found to increase with age (standardised β = 0.07 and 0.01) and to do so more rapidly in males compared to females. Additionally, the epigenetic CRP score had higher test-retest reliability compared to serum CRP, indicating its enhanced temporal stability. Higher serum CRP was not found to be associated with poorer cognitive ability (standardised β = - 0.08 and - 0.05); however, a consistent negative association was identified between cognitive ability and the epigenetic CRP score in both cohorts (standardised β = - 0.15 and - 0.08). CONCLUSIONS:An epigenetic proxy of CRP may provide a more reliable signature of chronic inflammation, allowing for more accurate stratification of individuals, and thus clearer inference of associations with incident health outcomes.

journal_name

Clin Epigenetics

journal_title

Clinical epigenetics

authors

Stevenson AJ,McCartney DL,Hillary RF,Campbell A,Morris SW,Bermingham ML,Walker RM,Evans KL,Boutin TS,Hayward C,McRae AF,McColl BW,Spires-Jones TL,McIntosh AM,Deary IJ,Marioni RE

doi

10.1186/s13148-020-00903-8

subject

Has Abstract

pub_date

2020-07-27 00:00:00

pages

113

issue

1

eissn

1868-7075

issn

1868-7083

pii

10.1186/s13148-020-00903-8

journal_volume

12

pub_type

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