ArticleClinical epigenetics2015
An epigenetic map of age-associated autosomal loci in northern European families at high risk for the metabolic syndrome.
Article in Clinical epigenetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Identification and validation of seven new loci showing differential DNA methylation related to serum lipid profile: an epigenome-wide approach. The REGICOR study.Human molecular genetics · 2016Pooled it
- Ten Years of EWAS.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- Article
- Epigenetic pacemaker: closed form algebraic solutions.BMC genomics · 2020Article
- Age-related DNA hydroxymethylation is enriched for gene expression and immune system processes in human peripheral blood.Epigenetics · 2020Article
- Article
- Critical evaluation of linear regression models for cell-subtype specific methylation signal from mixed blood cell DNA.PloS one · 2018Article
- Adipose tissue inflammation andClinical epigenetics · 2018Article
- H558R, a common SCN5A polymorphism, modifies the clinical phenotype of Brugada syndrome by modulating DNA methylation of SCN5A promoters.Journal of biomedical science · 2017Article
- Article
- Non-linear patterns in age-related DNA methylation may reflect CD4Epigenetics · 2017Article
- Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus.Epigenetics · 2017Review
- Article
- DNA methylation and obesity traits: An epigenome-wide association study. The REGICOR study.Epigenetics · 2017Article
- Epigenome-wide association study of triglyceride postprandial responses to a high-fat dietary challenge.Journal of lipid research · 2016Article
- Methylation of SOCS3 is inversely associated with metabolic syndrome in an epigenome-wide association study of obesity.Epigenetics · 2016Article
- Enlarged leukocyte referent libraries can explain additional variance in blood-based epigenome-wide association studies.Epigenomics · 2016Article
- Epigenetics of Aging.Current genomics · 2015Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe prevalence of chronic diseases such as cancer, type 2 diabetes, metabolic syndrome (MetS), and cardiovascular disease increases with age in all populations. Epigenetic features are hypothesized to play important roles in the pathophysiology of age-associated diseases, but a map of these markers is lacking. We searched for genome-wide age-associated methylation signatures in peripheral blood of individuals at high risks for MetS by profiling 485,000 CpG sites in 192 individuals of Northern European ancestry using the Illumina HM450 array. Subjects (ages 6-85 years) were part of seven extended families, and 73% of adults and 32% of children were overweight or obese.
resultsWe found 22,122 genome-wide significant age-associated CpG sites (P α=0.05 = 3.65 × 10(-7) after correction for multiple testing) of which 14,155 are positively associated with age while 7,967 are negatively associated. By applying a positional density-based clustering algorithm, we generated a map of epigenetic 'hot-spots' of age-associated genomic segments, which include 290 age-associated differentially methylated CpG clusters (aDMCs), of which 207 are positively associated with age. Gene/pathway enrichment analyses were performed on these clusters using FatiGO. Genes localized to both the positively (n = 241) and negatively (n = 16) age-associated clusters are significantly enriched in specific KEGG pathways and GO terms. The most significantly enriched pathways are the hedgehog signaling pathway (adjusted P = 3.96 × 10(-3)) and maturity-onset diabetes of the young (MODY) (adjusted P = 6.26 × 10(-3)) in the positive aDMCs and type I diabetes mellitus (adjusted P = 3.69 × 10(-7)) in the negative aDMCs. We also identified several epigenetic loci whose age-associated change rates differ between subjects diagnosed with MetS and those without.
conclusionWe conclude that in a family cohort at high risk for MetS, age-associated epigenetic features enrich in biological pathways important for determining the fate of fat cells and for insulin production. We also observe that several genes known to be related to MetS show differential epigenetic response to age in individuals with and without MetS.
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