Projects per year
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.
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.
Original language | English |
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Pages (from-to) | 1-8 |
Journal | Clinical Epigenetics |
Volume | 11 |
Issue number | 23 |
Early online date | 8 Feb 2019 |
DOIs | |
Publication status | Published - Feb 2019 |
Keywords / Materials (for Non-textual outputs)
- mortality
- epigenome-wide association study
- aging
- DNA methylation
- old cohorts
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Dive into the research topics of 'DNA methylome profiling of all-cause mortality in comparison with age-associated methylation patterns'. Together they form a unique fingerprint.Projects
- 3 Finished
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The Disconnected Mind Phase 3
Wardlaw, J. (Principal Investigator)
1/04/16 → 30/09/20
Project: Research
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RA2662 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2.
Porteous, D. (Principal Investigator)
1/09/13 → 31/08/19
Project: Research
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A genome wide association study of non pathological cognitive ageing
Deary, I. (Principal Investigator), Porteous, D. (Co-investigator) & Tenesa, A. (Co-investigator)
1/09/08 → 31/08/10
Project: Research