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DNA methylome profiling of all-cause mortality in comparison with age-associated methylation patterns

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  • Jesper Lund
  • Shuxia Li
  • Jan Baumbach
  • Anne Marie Svane
  • Jacob Hjelmborg
  • Lene Christiansen
  • Kaare Christensen
  • Paul Redmond
  • Riccardo Marioni
  • Ian Deary
  • Qihua Tan

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Original languageEnglish
Pages (from-to)1-8
JournalClinical Epigenetics
Volume11
Issue number23
Early online date8 Feb 2019
DOIs
Publication statusPublished - Feb 2019

Abstract

Background: Multiple epigenome-wide association studies have been performed to identify DNA methylation patterns regulated by aging or correlated with risk of death. However, the inter-relatedness of the epigenetic basis of aging and mortality has not been well investigated.


Methods: Using genome-wide DNA methylation data from the Lothian Birth Cohorts, we conducted a genome-wide association analysis of all-cause mortality and compared this with age-associated methylation patterns reported on the same samples. 

Results: Survival analysis using Cox-regression model identified 2,552 CpG sites with genome-wide significance (false discovery rate<0.05) for all-cause mortality. CpGs whose methylation levels are associated with increased mortality appear more distributed from the gene body to the intergenic regions whereas CpGs whose methylation levels are associated with decreased mortality is more concentrated at the promoter regions. In comparison with reported CpGs displaying significant age-dependent methylation patterns in the same samples, we observed a limited but highly significant overlap between mortality-associated and age-associated CpGs (p-value 2.52e-06). Most importantly, the overlapping CpGs are dominated by those whose overall age-related methylation patterns reduce the risk of death.

Conclusion:
All-cause mortality is significantly associated with altered methylation at multiple genomic sites with differential distribution in gene regions for CpGs correlated with increased or decreased risk of death. The age-dependent methylation changes could reflect an active response to the aging process that contributes to maintain individual survival.

    Research areas

  • mortality, epigenome-wide association study, aging, DNA methylation, old cohorts

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