DNA methylation age and perceived age in elderly Danish twins

Debrabant, Birgit; Soerensen, Mette; Christiansen, Lene; Tan, Qihua; Christensen, Kaare; Hjelmborg, Jacob

doi:10.1016/j.mad.2017.09.004

Cited by 16 publications

(8 citation statements)

References 30 publications

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“…A further 21 studies were excluded because they did not measure an appropriate outcome. For example, 14 did not measure a disease outcome, mortality, or longevity [41–54], 1 study investigated prevalent, not incident, diabetes [55], 2 studies examined physical frailty [44, 56], 3 studies focused on ageing-related genetic conditions [57–59] and 1 on twin differences [60]. Finally, one study was excluded because it was subsequently found to be a duplicate [61].…”

Section: Resultsmentioning

confidence: 99%

The epigenetic clock as a predictor of disease and mortality risk: a systematic review and meta-analysis

et al. 2019

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Background Ageing is one of the principal risk factors for many chronic diseases. However, there is considerable between-person variation in the rate of ageing and individual differences in their susceptibility to disease and death. Epigenetic mechanisms may play a role in human ageing, and DNA methylation age biomarkers may be good predictors of age-related diseases and mortality risk. The aims of this systematic review were to identify and synthesise the evidence for an association between peripherally measured DNA methylation age and longevity, age-related disease, and mortality risk. Methods A systematic search was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using relevant search terms, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and PsychINFO databases were searched to identify articles meeting the inclusion criteria. Studies were assessed for bias using Joanna Briggs Institute critical appraisal checklists. Data was extracted from studies measuring age acceleration as a predictor of age-related diseases, mortality or longevity, and the findings for similar outcomes compared. Using Review Manager 5.3 software, two meta-analyses (one per epigenetic clock) were conducted on studies measuring all-cause mortality. Results Twenty-three relevant articles were identified, including a total of 41,607 participants. Four studies focused on ageing and longevity, 11 on age-related disease (cancer, cardiovascular disease, and dementia), and 11 on mortality. There was some, although inconsistent, evidence for an association between increased DNA methylation age and risk of disease. Meta-analyses indicated that each 5-year increase in DNA methylation age was associated an 8 to 15% increased risk of mortality. Conclusion Due to the small number of studies and heterogeneity in study design and outcomes, the association between DNA methylation age and age-related disease and longevity is inconclusive. Increased epigenetic age was associated with mortality risk, but positive publication bias needs to be considered. Further research is needed to determine the extent to which DNA methylation age can be used as a clinical biomarker. Electronic supplementary material The online version of this article (10.1186/s13148-019-0656-7) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

The epigenetic clock as a predictor of disease and mortality risk: a systematic review and meta-analysis

et al. 2019

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“…Blood cell type composition was measured for most MADT and BWD participants and this was used for imputing the proportion of basophils, eosinophils, monocytes, neutrophils, and lymphocytes in the remaining individuals (see [ 18 ] for details). The methylation beta values were corrected for batch effects and cell types using a linear mixed model with sex, age, dataset, and cell type proportions as fixed effects and with sample plate and plate position as random effects.…”

Section: Methodsmentioning

confidence: 99%

DNA Methylation and All-Cause Mortality in Middle-Aged and Elderly Danish Twins

Svane

Soerensen

Lund

et al. 2018

Genes

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Several studies have linked DNA methylation at individual CpG sites to aging and various diseases. Recent studies have also identified single CpGs whose methylation levels are associated with all-cause mortality. In this study, we perform an epigenome-wide study of the association between CpG methylation and mortality in a population of 435 monozygotic twin pairs from three Danish twin studies. The participants were aged 55–90 at the time of blood sampling and were followed for up to 20 years. We validated our results by comparison with results from a British and a Swedish cohort, as well as results from the literature. We identified 2806 CpG sites associated with mortality (false discovery rate (FDR)<0.05), of which 24 had an association p-value below 10−7. This was confirmed by intra-pair comparison controlling for confounding effects. Eight of the 24 top sites could be validated in independent datasets or confirmed by previous studies. For all these eight sites, hypomethylation was associated with poor survival prognosis, and seven showed monozygotic correlations above 35%, indicating a potential moderate to strong heritability, but leaving room for substantial shared or unique environmental effects. We also set up a predictor for mortality using least absolute shrinkage and selection operator (LASSO) regression. The predictor showed good performance on the Danish data under cross-validation, but did not perform very well in independent samples.

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“…Genome-wide methylation data created using the Illumina Infinium HumanMethylation450K BeadChip are available for 155 LSADT-97 twin pairs and 246 MADT-08 twin pairs. The methylation data have been used in multiple epigenetic studies (e.g., Bolund et al, 2017;Debrabant et al, 2018;Lund et al, 2019;Starnawska et al, 2017;Svane et al, 2018). Methylation data have mainly been made for MZ twin pairs, but for 43 twin pairs (18 MZ and 25 DZ twin pairs) repeated methylation data were made both at baseline (LSADT-97) and follow-up (LSADT-07; Christiansen et al, 2016;Tan et al, 2016).…”

Section: Molecular Datamentioning

confidence: 99%

The Danish Twin Registry: An Updated Overview

et al. 2019

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The Danish Twin Registry (DTR) was established in the 1950s, when twins born from 1870 to 1910 were ascertained, and has since been extended to include twins from birth cohorts until 2009. The DTR currently comprises of more than 175,000 twins from the 140 birth cohorts. This makes the DTR the oldest nationwide twin register and among the largest in the world. The combination of data from several surveys, including biological samples and repeated measurements on the same individuals, and data from Danish national registers provides a unique resource for a wide range of twin studies. This article provides an updated overview of the data in the DTR: First, we provide a summary of the establishment of the register, the different ascertainment methods and the twins included; then follows an overview of major surveys conducted in the DTR since 1994 and a description of the DTR biobank, including a description of the molecular data created so far; finally, a short description is given of the linkage to Danish national registers at Statistics Denmark and some recent examples of studies using the various data resources in the DTR are highlighted.

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DNA methylation age and perceived age in elderly Danish twins

Cited by 16 publications

References 30 publications

The epigenetic clock as a predictor of disease and mortality risk: a systematic review and meta-analysis

The epigenetic clock as a predictor of disease and mortality risk: a systematic review and meta-analysis

DNA Methylation and All-Cause Mortality in Middle-Aged and Elderly Danish Twins

The Danish Twin Registry: An Updated Overview

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