DNA methylation age acceleration and risk factors for Alzheimer’s disease

Daniel L. McCartney; Anna J. Stevenson; Rosie May Walker; Jude Gibson; Stewart W. Morris; Archie I Campbell; Alison D. Murray; Heather Clare Whalley; David John Porteous; Andrew Mark McIntosh; Kathryn Louise Evans; Ian J. Deary; Riccardo Emilio Marioni

doi:10.1016/j.dadm.2018.05.006

GenomicsAlzheimer s & Dementia Diagnosis Assessment & Disease MonitoringJan 1, 2018

Peer-reviewed journal article

DNA methylation age acceleration and risk factors for Alzheimer’s disease

Daniel L. McCartney iD, Anna J. Stevenson iD, Rosie May Walker iD, Jude Gibson iD, Stewart W. Morris, Archie I Campbell iD, Alison D. Murray iD, Heather Clare Whalley iD, David John Porteous iD, Andrew Mark McIntosh iD, Kathryn Louise Evans iD, Ian J. Deary iD, Riccardo Emilio Marioni iD

Abstract

INTRODUCTIONThe epigenetic clock is a DNA methylation-based estimate of biological age and is correlated with chronological age - the greatest risk factor for Alzheimers disease (AD). Genetic and environmental risk factors exist for AD, several of which are potentially modifiable. Here, we assess the relationship associations between the epigenetic clock and AD risk factors.\n\nMETHODSLinear mixed modelling was used to assess the relationship between age acceleration (the residual of biological age regressed onto chronological age) and AD risk factors relating to cognitive reserve, lifestyle, disease, and genetics in the Generation Scotland study (n=5,100).\n\nRESULTSWe report significant associations between the epigenetic clock and BMI, total:HDL cholesterol ratios, socioeconomic status, and smoking behaviour (Bonferroni-adjusted P<0.05).\n\nDISCUSSIONAssociations are present between environmental risk factors for AD and age acceleration. Measures to modify such risk factors might improve the risk profile for AD and the rate of biological ageing. Future longitudinal analyses are therefore warranted.

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