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.


CONCLUSIONS
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.
Department of Twin Research & Genetic Epidemiology, King's College London, London, UK. christopher.g.bell@kcl.ac.uk.|MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK. christopher.g.bell@kcl.ac.uk.|Human Development and Health Academic Unit, Institute of Developmental Sciences, University of Southampton, Southampton, UK. christopher.g.bell@kcl.ac.uk.|Epigenomic Medicine, Biological Sciences, Faculty of Environmental and Natural Sciences, University of Southampton, Southampton, UK. christopher.g.bell@kcl.ac.uk.
Christopher G
CG
Bell
BGI-Shenzhen, Shenzhen, 518083, China.
Yudong
Y
Xia
Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.|Institute of Cancer Research, Sutton, UK.
Wei
W
Yuan
BGI-Shenzhen, Shenzhen, 518083, China.
Fei
F
Gao
Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.
Kirsten
K
Ward
Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.
Leonie
L
Roos
Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.
Massimo
M
Mangino
Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.
Pirro G
PG
Hysi
Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.
Jordana
J
Bell
BGI-Shenzhen, Shenzhen, 518083, China.
Jun
J
Wang
Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.
Timothy D
TD
Spector
Ageing; Common Disease; DNA methylation; Epigenetics; Human
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