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Novel regional age-associated DNA methylation changes within human common disease-associated loci

Novel regional age-associated DNA methylation changes within human common disease-associated loci
Novel regional age-associated DNA methylation changes within human common disease-associated loci
Background: Advancing age progressively impacts on risk and severity of chronic disease. It also modifies the epigenome, with changes in DNA methylation, due to both random drift and variation within specific functional loci.

Results: In a discovery set of 2238 peripheral-blood genome-wide DNA methylomes aged 19–82 years, we identify 71 age-associated differentially methylated regions within the linkage disequilibrium blocks of the single nucleotide polymorphisms from the NIH genome-wide association study catalogue. This included 52 novel regions, 29 within loci not covered by 450 k or 27 k Illumina array, and with enrichment for DNase-I Hypersensitivity sites across the full range of tissues. These age-associated differentially methylated regions also show marked enrichment for enhancers and poised promoters across multiple cell types. In a replication set of 2084 DNA methylomes, 95.7 % of the age-associated differentially methylated regions showed the same direction of ageing effect, with 80.3 % and 53.5 % replicated to p?<?0.05 and p?<?1.85?×?10–8, respectively.

Conclusion: By analysing the functionally enriched disease and trait-associated regions of the human genome, we identify novel epigenetic ageing changes, which could be useful biomarkers or provide mechanistic insights into age-related common diseases.
1465-6906
1-14
Bell, Christopher G.
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Xia, Yudong
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Yuan, Wei
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Gao, Fei
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Ward, Kirsten
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Roos, Leonie
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Mangino, Massimo
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Hysi, Pirro
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Bell, Jordana
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Wang, Jun
dac45864-634f-41ec-ba2a-1e59ad23ae97
Spector, Tim
b8289355-8b82-4ec4-bfd7-56e85af732ca
Bell, Christopher G.
44982df7-0746-4cdb-bed1-0bdfe68f1a64
Xia, Yudong
1a3cbe01-cb90-4144-939f-ab2c72779f12
Yuan, Wei
934197a6-0708-4967-ab09-032f8327e4e5
Gao, Fei
fa3e4707-8319-49fa-897b-b27f7a534508
Ward, Kirsten
0d581684-6bdd-40a6-9cad-ec46bf82ed47
Roos, Leonie
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Mangino, Massimo
19ad1660-3639-45a8-93d6-e6a9b5c1c64b
Hysi, Pirro
ec24947f-5c59-4ffd-af5a-9d5bdf2b80ec
Bell, Jordana
48ac3b6f-cc9f-4311-b683-c8fa862c03c1
Wang, Jun
dac45864-634f-41ec-ba2a-1e59ad23ae97
Spector, Tim
b8289355-8b82-4ec4-bfd7-56e85af732ca

Bell, Christopher G., Xia, Yudong, Yuan, Wei, Gao, Fei, Ward, Kirsten, Roos, Leonie, Mangino, Massimo, Hysi, Pirro, Bell, Jordana, Wang, Jun and Spector, Tim (2016) Novel regional age-associated DNA methylation changes within human common disease-associated loci. Genome Biology, 17 (193), 1-14. (doi:10.1186/s13059-016-1051-8).

Record type: Article

Abstract

Background: Advancing age progressively impacts on risk and severity of chronic disease. It also modifies the epigenome, with changes in DNA methylation, due to both random drift and variation within specific functional loci.

Results: In a discovery set of 2238 peripheral-blood genome-wide DNA methylomes aged 19–82 years, we identify 71 age-associated differentially methylated regions within the linkage disequilibrium blocks of the single nucleotide polymorphisms from the NIH genome-wide association study catalogue. This included 52 novel regions, 29 within loci not covered by 450 k or 27 k Illumina array, and with enrichment for DNase-I Hypersensitivity sites across the full range of tissues. These age-associated differentially methylated regions also show marked enrichment for enhancers and poised promoters across multiple cell types. In a replication set of 2084 DNA methylomes, 95.7 % of the age-associated differentially methylated regions showed the same direction of ageing effect, with 80.3 % and 53.5 % replicated to p?<?0.05 and p?<?1.85?×?10–8, respectively.

Conclusion: By analysing the functionally enriched disease and trait-associated regions of the human genome, we identify novel epigenetic ageing changes, which could be useful biomarkers or provide mechanistic insights into age-related common diseases.

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More information

Accepted/In Press date: 31 August 2016
e-pub ahead of print date: 23 September 2016
Published date: 23 September 2016
Organisations: Human Development & Health, Centre for Biological Sciences, MRC Life-Course Epidemiology Unit

Identifiers

Local EPrints ID: 400750
URI: https://eprints.soton.ac.uk/id/eprint/400750
ISSN: 1465-6906
PURE UUID: 551d8a1f-69de-4877-8b77-7b51d7f24c67
ORCID for Christopher G. Bell: ORCID iD orcid.org/0000-0003-4601-1242

Catalogue record

Date deposited: 26 Sep 2016 10:02
Last modified: 19 Jul 2019 19:44

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