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

Jesper Lund, S. Li, J. Baumbach, Anne Marie Svane, J. B. Hejlmborg, Lene Christiansen, Kaare Christensen, P. Redmond, R. E. Marioni, I. J. Deary, Quiha Tan

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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 the Cox regression model identified 2552 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.
OriginalsprogEngelsk
TidsskriftClinical Epigenetics
Vol/bind11
Udgave nummer23
Antal sider8
ISSN1868-7075
DOI
StatusUdgivet - 2019
Udgivet eksterntJa

Fingerprint

DNA Fingerprinting
Methylation
Mortality
DNA Methylation
Genome
Intergenic DNA
Genome-Wide Association Study
Survival Analysis
Proportional Hazards Models
Genetic Promoter Regions
Epigenomics
Genes
Parturition

Citer dette

Lund, Jesper ; Li, S. ; Baumbach, J. ; Svane, Anne Marie ; Hejlmborg, J. B. ; Christiansen, Lene ; Christensen, Kaare ; Redmond, P. ; Marioni, R. E. ; Deary, I. J. ; Tan, Quiha. / DNA methylome profiling of all-cause mortality in comparison with age-associated methylation patterns. I: Clinical Epigenetics. 2019 ; Bind 11, Nr. 23.
@article{4f7b6c4bdd6a4814858976c6c70d2204,
title = "DNA methylome profiling of all-cause mortality in comparison with age-associated methylation patterns",
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 the Cox regression model identified 2552 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.",
author = "Jesper Lund and S. Li and J. Baumbach and Svane, {Anne Marie} and Hejlmborg, {J. B.} and Lene Christiansen and Kaare Christensen and P. Redmond and Marioni, {R. E.} and Deary, {I. J.} and Quiha Tan",
year = "2019",
doi = "10.1186/s13148-019-0622-4",
language = "English",
volume = "11",
journal = "Clinical Epigenetics (Print)",
issn = "1868-7075",
publisher = "BioMed Central",
number = "23",

}

Lund, J, Li, S, Baumbach, J, Svane, AM, Hejlmborg, JB, Christiansen, L, Christensen, K, Redmond, P, Marioni, RE, Deary, IJ & Tan, Q 2019, 'DNA methylome profiling of all-cause mortality in comparison with age-associated methylation patterns' Clinical Epigenetics, bind 11, nr. 23. https://doi.org/10.1186/s13148-019-0622-4

DNA methylome profiling of all-cause mortality in comparison with age-associated methylation patterns. / Lund, Jesper; Li, S.; Baumbach, J.; Svane, Anne Marie; Hejlmborg, J. B. ; Christiansen, Lene ; Christensen, Kaare; Redmond, P.; Marioni, R. E.; Deary, I. J. ; Tan, Quiha.

I: Clinical Epigenetics, Bind 11, Nr. 23, 2019.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - DNA methylome profiling of all-cause mortality in comparison with age-associated methylation patterns

AU - Lund, Jesper

AU - Li, S.

AU - Baumbach, J.

AU - Svane, Anne Marie

AU - Hejlmborg, J. B.

AU - Christiansen, Lene

AU - Christensen, Kaare

AU - Redmond, P.

AU - Marioni, R. E.

AU - Deary, I. J.

AU - Tan, Quiha

PY - 2019

Y1 - 2019

N2 - 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 the Cox regression model identified 2552 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.

AB - 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 the Cox regression model identified 2552 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.

U2 - 10.1186/s13148-019-0622-4

DO - 10.1186/s13148-019-0622-4

M3 - Journal article

VL - 11

JO - Clinical Epigenetics (Print)

JF - Clinical Epigenetics (Print)

SN - 1868-7075

IS - 23

ER -