Investigating the relationship between DNA methylation age acceleration and risk factors for Alzheimer's disease

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  • Daniel L. McCartney
    Medical Genetics Section, Centre for Genomic and Experimental Medicine Institute of Genetics and Molecular Medicine, University of Edinburgh Edinburgh Scotland
  • Anna J. Stevenson
    Medical Genetics Section, Centre for Genomic and Experimental Medicine Institute of Genetics and Molecular Medicine, University of Edinburgh Edinburgh Scotland
  • Rosie M. Walker
    Medical Genetics Section, Centre for Genomic and Experimental Medicine Institute of Genetics and Molecular Medicine, University of Edinburgh Edinburgh Scotland
  • Jude Gibson
    Division of Psychiatry University of Edinburgh, Royal Edinburgh Hospital Edinburgh Scotland
  • Stewart W. Morris
    Medical Genetics Section, Centre for Genomic and Experimental Medicine Institute of Genetics and Molecular Medicine, University of Edinburgh Edinburgh Scotland
  • Archie Campbell
    Medical Genetics Section, Centre for Genomic and Experimental Medicine Institute of Genetics and Molecular Medicine, University of Edinburgh Edinburgh Scotland
  • Alison D. Murray
    Aberdeen Biomedical Imaging Centre University of Aberdeen Aberdeen Scotland
  • Heather C. Whalley
    Division of Psychiatry University of Edinburgh, Royal Edinburgh Hospital Edinburgh Scotland
  • David J. Porteous
    Medical Genetics Section, Centre for Genomic and Experimental Medicine Institute of Genetics and Molecular Medicine, University of Edinburgh Edinburgh Scotland
  • Andrew M. McIntosh
    Medical Genetics Section, Centre for Genomic and Experimental Medicine Institute of Genetics and Molecular Medicine, University of Edinburgh Edinburgh Scotland
  • Kathryn L. Evans
    Medical Genetics Section, Centre for Genomic and Experimental Medicine Institute of Genetics and Molecular Medicine, University of Edinburgh Edinburgh Scotland
  • Ian J. Deary
    Centre for Cognitive Ageing and Cognitive Epidemiology University of Edinburgh Edinburgh Scotland
  • Riccardo E. Marioni
    Medical Genetics Section, Centre for Genomic and Experimental Medicine Institute of Genetics and Molecular Medicine, University of Edinburgh Edinburgh Scotland

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<jats:title>Abstract</jats:title><jats:sec><jats:title>Introduction</jats:title><jats:p>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. In this study, we assess the relationship between the epigenetic clock and AD risk factors.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Multilevel models were 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 = 5100).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We report significant associations between age acceleration and body mass index, total cholesterol to high‐density lipoprotein cholesterol ratios, socioeconomic status, high blood pressure, and smoking behavior (Bonferroni‐adjusted <jats:italic>P</jats:italic> < .05).</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>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.</jats:p></jats:sec>

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