A meta-analysis of genome-wide association studies of epigenetic age acceleration

Jude Gibson, Tom C. Russ, Toni-Kim Clarke, David M. Howard, Robert F. Hillary, Kathryn L. Evans, Rosie M. Walker, Mairead L. Bermingham, Stewart W. Morris, Archie Campbell, Caroline Hayward, Alison D. Murray, David J. Porteous, Steve Horvath, Ake T. Lu, Andrew M. McIntosh, Heather C. Whalley, Riccardo E. Marioni* (Corresponding Author)

*Corresponding author for this work

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Abstract

Author summary DNA methylation, an epigenetic process, is known to vary with age. Methylation levels at specific sites across the genome can be combined to form estimates of age known as ‘epigenetic age’. The difference between epigenetic age and chronological age is referred to as ‘epigenetic age acceleration’, with positive values indicating that a person is biologically older than their years. Understanding why some people seem to age faster than others could shed light on the biological processes behind age-related decline; however, the mechanisms underlying differential rates of epigenetic ageing are largely unknown. Here, we investigate genetic determinants of two commonly used epigenetic age acceleration measures, based on the Horvath and Hannum epigenetic clocks. We report novel genetic variants and genes associated with epigenetic age acceleration, and highlight differences in the genetic factors influencing these two measures. We identify ten genetic variants and 21 genes associated with Horvath-based epigenetic age acceleration, and one variant and 12 genes associated with the Hannum-based measure. There were no genome-wide significant variants or genes in common between the Horvath-based and Hannum-based measures, supporting the hypothesis that they represent different aspects of ageing. Our results suggest a partial genetic basis underlying some previously reported phenotypic associations.
Original languageEnglish
Article numbere1008104
Number of pages30
JournalPLoS Genetics
Volume15
Issue number11
Early online date18 Nov 2019
DOIs
Publication statusPublished - Nov 2019

Keywords

  • DNA methylation
  • ageing
  • sexual dimorphism
  • X-chromosome
  • Generation Scotland

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics
  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Cancer Research

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    Gibson, J., Russ, T. C., Clarke, T-K., Howard, D. M., Hillary, R. F., Evans, K. L., Walker, R. M., Bermingham, M. L., Morris, S. W., Campbell, A., Hayward, C., Murray, A. D., Porteous, D. J., Horvath, S., Lu, A. T., McIntosh, A. M., Whalley, H. C., & Marioni, R. E. (2019). A meta-analysis of genome-wide association studies of epigenetic age acceleration. PLoS Genetics, 15(11), [e1008104]. https://doi.org/10.1371/journal.pgen.1008104