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

Daniel L McCartney, Anna J Stevenson, Rosie M 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 (Corresponding Author)

Research output: Contribution to journalArticlepeer-review

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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. In this study, we assess the relationship between the epigenetic clock and AD risk factors.

Methods: 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).

Results: 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 P < .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.

Original languageEnglish
Pages (from-to)429-437
Number of pages9
JournalAlzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Early online date21 Jun 2018
Publication statusPublished - 2018

Bibliographical note

This work was supported by a Alzheimer's Research UK Major Project grant (ARUK-PG2017B-10). Generation Scotland received core funding from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006). We are grateful to all the families who took part, the general practitioners and the Scottish School of Primary Care for their help in recruiting them, and the whole Generation Scotland team that includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, health-care assistants and nurses. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland, and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” [STRADL];104036/Z/14/Z). DNA methylation data collection was funded by the Wellcome Trust Strategic Award (10436/Z/14/Z). The research was conducted in the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE), part of the cross-council Lifelong Health and Wellbeing Initiative (MR/K026992/1); funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged. CCACE supports I.J.D. with some additional support from the Dementias Platform UK (MR/L015382/1). A.M.M. and H.C.W. have received support from the Sackler Institute.


  • Epigenetic clock
  • Alzheimer's disease
  • genetics
  • Generation Scotland


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