Novel regional age-associated DNA methylation changes within human common disease-associated loci
File(s)
Published version
Author(s)
Type
Journal 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.
Date Issued
2016-09-23
Date Acceptance
2016-08-31
Citation
Genome Biology, 2016, 17
ISSN
1474-760X
Publisher
BioMed Central
Journal / Book Title
Genome Biology
Volume
17
Copyright Statement
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
License URL
Subjects
Ageing
Common Disease
DNA methylation
Epigenetics
Human
Bioinformatics
05 Environmental Sciences
06 Biological Sciences
08 Information And Computing Sciences
Publication Status
Published
Article Number
193