King's College London

Research portal

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

Research output: Contribution to journalArticlepeer-review

Christopher G. Bell, Yudong Xia, Wei Yuan, Fei Gao, Kirsten Ward, Leonie Roos, Massimo Mangino, Pirro G. Hysi, Jordana Bell, Jun Wang, Timothy D. Spector

Original languageEnglish
Article number193
Pages (from-to)193
JournalGenome Biology
Volume17
Issue number1
DOIs
Accepted/In press31 Aug 2016
Published23 Sep 2016

Documents

King's Authors

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.

Download statistics

No data available

View graph of relations

© 2020 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454