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

By Daniel L McCartney, Anna J Stevenson, Rosie Walker, Jude Gibson, Stewart W Morris, Archie Campbell, Alison D Murray, Heather C. Whalley, David J Porteous, Andrew M McIntosh, Kathryn L Evans, Ian J Deary, Riccardo E Marioni

Posted 08 Mar 2018
bioRxiv DOI: 10.1101/278945 (published DOI: 10.1016/j.dadm.2018.05.006)

INTRODUCTION: The 'epigenetic clock' is a DNA methylation based estimate of biological age and is correlated with chronological age: the greatest risk factor for Alzheimer's 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. METHODS: Linear 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). RESULTS: We report significant associations between the epigenetic clock and BMI, total:HDL cholesterol ratios, socioeconomic status, and smoking behaviour (Bonferroni adjusted P<0.05). DISCUSSION: Associations 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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