Identification, replication and characterization of epigenetic remodelling in the aging genome: A cross population analysis

Shuxia Li; Lene Christiansen; Kaare Christensen; Torben A Kruse; Paul Redmond; Riccardo Marioni; Ian Deary; Qihua Tan

doi:10.1038/s41598-017-08346-7

Identification, replication and characterization of epigenetic remodelling in the aging genome: A cross population analysis

Shuxia Li, Lene Christiansen, Kaare Christensen, Torben A Kruse, Paul Redmond, Riccardo Marioni, Ian Deary, Qihua Tan

Research output: Contribution to journal › Article › peer-review

Abstract

Aging is a complex biological process regulated by multiple cellular pathways and molecular mechanisms including epigenetics. Using genome-wide DNA methylation data measured in a large collection of Scottish old individuals, we performed discovery association analysis to identify age-methylated CpGs and replicated them in two independent Danish cohorts. The double-replicated CpGs were characterized by distribution over gene regions and location in relation to CpG islands. The replicated CpGs were further characterized by involvement in biological pathways to study their functional implications in aging. We identified 67,604 age-associated CpG sites reaching genome-wide significance of FWER<0.05, 86% demethylated with increasing age. Double-replication resulted in 5,168 CpGs (39% age-methylated and 61% age-demethylated) which were characterized by high concentration of age-methylated CpGs at 1stExon and TSS200 and a dominant pattern of age-demethylated CpGs at other gene regions, and by overwhelming age-related methylation in CpG islands and demethylation at shore/shelf and open sea. The differential distribution patterns over gene regions for methylated and demethylated CpGs both relate to reduced gene activity during aging. Pathway analysis showed that age-dependent methylations were especially involved in cellular signalling activities while demethylations particularly linked to functions of the extracellular matrix, all implicated in the aging process and age-related disease risk

Original language	English
Article number	8183
Pages (from-to)	1-8
Journal	Scientific Reports
Volume	7
Early online date	15 Aug 2017
DOIs	https://doi.org/10.1038/s41598-017-08346-7
Publication status	E-pub ahead of print - 15 Aug 2017

Keywords / Materials (for Non-textual outputs)

aging
DNA methylation
association analysis
genomic location
pathway analysis

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10.1038/s41598-017-08346-7

ShuxiaEtalSR2017IdentificationReplicationAndCharacterizationOfEpigeneticFinal published version, 1.83 MBLicence: Creative Commons: Attribution (CC-BY)

The Disconnected Mind Phase 3
Cox, S. (Principal Investigator) & Deary, I. (Co-investigator)
1/04/16 → 31/03/23
Project: Research
RA2661 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2. Main Budget.
Deary, I. (Principal Investigator), Gale, C. (Co-investigator), Holmes, M. (Co-investigator), Logie, P. (Co-investigator), Maclullich, A. (Co-investigator), Porteous, D. (Co-investigator), Seckl, J. (Co-investigator), Starr, J. (Co-investigator), Wardlaw, J. (Co-investigator) & Okely, J. (Researcher)
1/09/13 → 31/08/19
Project: Research
A Hundred at Ninety: the common cause Hypothesis of Ageing tested in four waves of the Lothian Birth Cohort 1921
Deary, I. (Principal Investigator), Bates, T. (Co-investigator), Gow, A. (Co-investigator) & Starr, J. (Co-investigator)
UK central government bodies/local authorities, health and hospital authorities
1/01/11 → 31/12/12
Project: Research

Cite this

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title = "Identification, replication and characterization of epigenetic remodelling in the aging genome: A cross population analysis",

abstract = "Aging is a complex biological process regulated by multiple cellular pathways and molecular mechanisms including epigenetics. Using genome-wide DNA methylation data measured in a large collection of Scottish old individuals, we performed discovery association analysis to identify age-methylated CpGs and replicated them in two independent Danish cohorts. The double-replicated CpGs were characterized by distribution over gene regions and location in relation to CpG islands. The replicated CpGs were further characterized by involvement in biological pathways to study their functional implications in aging. We identified 67,604 age-associated CpG sites reaching genome-wide significance of FWER<0.05, 86% demethylated with increasing age. Double-replication resulted in 5,168 CpGs (39% age-methylated and 61% age-demethylated) which were characterized by high concentration of age-methylated CpGs at 1stExon and TSS200 and a dominant pattern of age-demethylated CpGs at other gene regions, and by overwhelming age-related methylation in CpG islands and demethylation at shore/shelf and open sea. The differential distribution patterns over gene regions for methylated and demethylated CpGs both relate to reduced gene activity during aging. Pathway analysis showed that age-dependent methylations were especially involved in cellular signalling activities while demethylations particularly linked to functions of the extracellular matrix, all implicated in the aging process and age-related disease risk",

keywords = "aging, DNA methylation, association analysis, genomic location, pathway analysis",

author = "Shuxia Li and Lene Christiansen and Kaare Christensen and Kruse, {Torben A} and Paul Redmond and Riccardo Marioni and Ian Deary and Qihua Tan",

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T2 - A cross population analysis

AU - Li, Shuxia

AU - Christiansen, Lene

AU - Christensen, Kaare

AU - Kruse, Torben A

AU - Redmond, Paul

AU - Marioni, Riccardo

AU - Deary, Ian

AU - Tan, Qihua

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N2 - Aging is a complex biological process regulated by multiple cellular pathways and molecular mechanisms including epigenetics. Using genome-wide DNA methylation data measured in a large collection of Scottish old individuals, we performed discovery association analysis to identify age-methylated CpGs and replicated them in two independent Danish cohorts. The double-replicated CpGs were characterized by distribution over gene regions and location in relation to CpG islands. The replicated CpGs were further characterized by involvement in biological pathways to study their functional implications in aging. We identified 67,604 age-associated CpG sites reaching genome-wide significance of FWER<0.05, 86% demethylated with increasing age. Double-replication resulted in 5,168 CpGs (39% age-methylated and 61% age-demethylated) which were characterized by high concentration of age-methylated CpGs at 1stExon and TSS200 and a dominant pattern of age-demethylated CpGs at other gene regions, and by overwhelming age-related methylation in CpG islands and demethylation at shore/shelf and open sea. The differential distribution patterns over gene regions for methylated and demethylated CpGs both relate to reduced gene activity during aging. Pathway analysis showed that age-dependent methylations were especially involved in cellular signalling activities while demethylations particularly linked to functions of the extracellular matrix, all implicated in the aging process and age-related disease risk

AB - Aging is a complex biological process regulated by multiple cellular pathways and molecular mechanisms including epigenetics. Using genome-wide DNA methylation data measured in a large collection of Scottish old individuals, we performed discovery association analysis to identify age-methylated CpGs and replicated them in two independent Danish cohorts. The double-replicated CpGs were characterized by distribution over gene regions and location in relation to CpG islands. The replicated CpGs were further characterized by involvement in biological pathways to study their functional implications in aging. We identified 67,604 age-associated CpG sites reaching genome-wide significance of FWER<0.05, 86% demethylated with increasing age. Double-replication resulted in 5,168 CpGs (39% age-methylated and 61% age-demethylated) which were characterized by high concentration of age-methylated CpGs at 1stExon and TSS200 and a dominant pattern of age-demethylated CpGs at other gene regions, and by overwhelming age-related methylation in CpG islands and demethylation at shore/shelf and open sea. The differential distribution patterns over gene regions for methylated and demethylated CpGs both relate to reduced gene activity during aging. Pathway analysis showed that age-dependent methylations were especially involved in cellular signalling activities while demethylations particularly linked to functions of the extracellular matrix, all implicated in the aging process and age-related disease risk

KW - aging

KW - DNA methylation

KW - association analysis

KW - genomic location

KW - pathway analysis

U2 - 10.1038/s41598-017-08346-7

DO - 10.1038/s41598-017-08346-7

M3 - Article

SN - 2045-2322

VL - 7

SP - 1

EP - 8

JO - Scientific Reports

JF - Scientific Reports

M1 - 8183

ER -

Identification, replication and characterization of epigenetic remodelling in the aging genome: A cross population analysis

Abstract

Keywords / Materials (for Non-textual outputs)

Access to Document

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Projects

The Disconnected Mind Phase 3

RA2661 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2. Main Budget.

A Hundred at Ninety: the common cause Hypothesis of Ageing tested in four waves of the Lothian Birth Cohort 1921

Cite this