Blood-based epigenetic estimators of chronological age in human adults using DNA methylation data from the Illumina MethylationEPIC array

Abstract

Background Epigenetic clocks have been recognized for their precise prediction of chronological age, age-related diseases, and all-cause mortality. Existing epigenetic clocks are based on CpGs from the Illumina HumanMethylation450 BeadChip (450 K) which has now been replaced by the latest platform, Illumina MethylationEPIC BeadChip (EPIC). Thus, it remains unclear to what extent EPIC contributes to increased precision and accuracy in the prediction of chronological age. Results We developed three blood-based epigenetic clocks for human adults using EPIC-based DNA methylation (DNAm) data from the Norwegian Mother, Father and Child Cohort Study (MoBa) and the Gene Expression Omnibus (GEO) public repository: 1) an Adult Blood-based EPIC Clock (ABEC) trained on DNAm data from MoBa (n = 1592, age-span: 19 to 59 years), 2) an extended ABEC (eABEC) trained on DNAm data from MoBa and GEO (n = 2227, age-span: 18 to 88 years), and 3) a common ABEC (cABEC) trained on the same training set as eABEC but restricted to CpGs common to 450 K and EPIC. Our clocks showed high precision (Pearson correlation between chronological and epigenetic age (r) > 0.94) in independent cohorts, including GSE111165 (n = 15), GSE115278 (n = 108), GSE132203 (n = 795), and the Epigenetics in Pregnancy (EPIPREG) study of the STORK Groruddalen Cohort (n = 470). This high precision is unlikely due to the use of EPIC, but rather due to the large sample size of the training set. Conclusions Our ABECs predicted adults’ chronological age precisely in independent cohorts. As EPIC is now the dominant platform for measuring DNAm, these clocks will be useful in further predictions of chronological age, age-related diseases, and mortality.

A catalogue of omics biological ageing clocks reveals substantial commonality and associations with disease risk

“…We have tried to validate our omics ageing clocks trained in ORCADES in independent populations where available, to illustrate their wider applicability. A limitation faced by previous studies was the narrow age range of AGING individuals in the training sample, for example Lee et al's epigenetic clock trained in a pregnancy cohort produced extremely accurate estimations of chronAge for individuals under 45 but underestimated age in older individuals [52]. Our clocks avoid this limitation due to the wide age range (16-100) of individuals in the ORCADES cohort.…”

The Relationship between Epigenetic Age and Myocardial Infarction/Acute Coronary Syndrome in a Population-Based Nested Case-Control Study

“…Age is one of the strongest risk factors for many human diseases, including CVD and, specifically, CHD [16,24]. Given the significance of biological aging, a variety of estimators of biological age were constructed.…”

“…Hannum's Blood-based clock is based on 71 CpG sites [9], Horvath's Pan-Tissue clock is based on 353 CpG sites [12], Levine's PhenoAge clock is based on 513 CpG sites capturing age-related and functional phenotype modifications [13] and Horvath's Skin and Blood clock is based on 391 CpGs for human fibroblasts and other cell types [14]. Further to these, over 30 epigenetic clocks have been published [15], including those recently developed on the base of the Illumina Methylation EPIC 850 BeadChip (850 K) [16].…”

A catalogue of omics biological ageing clocks reveals substantial commonality and associations with disease risk

“…We have tried to validate our omics ageing clocks trained in ORCADES in independent populations where available, to illustrate their wider applicability. A limitation faced by previous studies was the narrow age range of individuals in the training sample, for example Lee et al’s epigenetic clock trained in a pregnancy cohort produced extremely accurate estimations of chronAge for individuals under 45 but underestimated age in older individuals 51 . Our clocks avoid this limitation due to the wide age range (16-100) of individuals in the ORCADES cohort.…”