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dc.date.accessioned2018-07-05T10:40:21Z
dc.date.issued2016
dc.identifierhttp://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-1051-8
dc.identifier.citationGENOME BIOLOGY, 2016, 17
dc.identifier.issn1474-760X
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1995
dc.description.abstractBackground: 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 x 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.
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectEpigenetics DNA methylation Ageing Common Disease Human GENOME-WIDE ASSOCIATION EMBRYONIC STEM-CELLS CPG ISLAND SHORES EPIGENETIC VARIATION REGULATORY REGIONS GENETIC-VARIATION ENCODE DATA METHYLOME CANCER BLOOD
dc.titleNovel regional age-associated DNA methylation changes within human common disease-associated loci
dc.typeJournal Article
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2016
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfGENOME BIOLOGY
pubs.notesISI Document Delivery No.: DX5ZT Times Cited: 0 Cited Reference Count: 90 Bell, Christopher G. Xia, Yudong Yuan, Wei Gao, Fei Ward, Kirsten Roos, Leonie Mangino, Massimo Hysi, Pirro G. Bell, Jordana Wang, Jun Spector, Timothy D. European Research Council [250157]; BGI; Wellcome Trust; European Community; National Institute for Health Research (NIHR)-BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust; King's College London; MRC Lifecourse Epidemiology Unit; EpiGen Global Research Consortium; ERC Funding support for this project was obtained from the European Research Council (project number 250157) and BGI. TwinsUK received funding from the Wellcome Trust; European Community's Seventh Framework Programme (FP7/2007-2013), the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. SNP genotyping was performed by The Wellcome Trust Sanger Institute and National Eye Institute via NIH/CIDR. CGB receives support from the MRC Lifecourse Epidemiology Unit and the EpiGen Global Research Consortium (www.epigengrc.com). TDS is holder of an ERC Advanced Principal Investigator award. 0 BIOMED CENTRAL LTD LONDON GENOME BIOL public 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 x 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.
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers
pubs.volume17
pubs.embargo.termsNot known
icr.researchteamCancer Biomarkersen_US
dc.contributor.icrauthorYuan, Weien


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