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

Yunsung Lee,Maria C Magnus,Per Magnus,Robert Lyle,Astanand Jugessur,Christian M Page,Haakon E Nustad,Jon Bohlin,Sindre Lee-Ødegård,Christine Sommer,Rashmi B Prasad,Line Sletner,Kristine L Haftorn,William R P Denault,Gunn-Helen Moen,Jennifer R Harris,Siri E Håberg,Håkon K Gjessing,Leif C Groop

doi:10.1186/s12864-020-07168-8

Abstract

BackgroundEpigenetic 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 Existing epigenetic clocks are based on CpGs from the Illumina HumanMethylation450 BeadChip (450 K) which has now been replaced by the latest platform, Illumina MethylationEPIC BeadChip (EPIC).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.ResultsWe 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.ConclusionsOur 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.

Highlights

Epigenetic clocks have been recognized for their precise prediction of chronological age, age-related diseases, and all-cause mortality
Epigenetic age is a linear combination of DNA methylation (DNAm) levels at specific CpGs, which are weighted by their respective coefficients estimated through an epigenetic clock
Most of the previously published epigenetic clocks were based on specific CpGs from the Illumina HumanMethylation450 BeadChip (450 K). This platform has recently been replaced by the Illumina MethylationEPIC BeadChip (EPIC)

Summary

Introduction

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 been replaced by the latest platform, Illumina MethylationEPIC BeadChip (EPIC). Most of the previously published epigenetic clocks (the Hannum Blood-based clock [19], Horvath Pan-tissue clock [20], Levine PhenoAge clock [16], and Horvath Skin & Blood clock [3]) were based on specific CpGs from the Illumina HumanMethylation450 BeadChip (450 K). This platform has recently been replaced by the Illumina MethylationEPIC BeadChip (EPIC). It remains unclear to what extent EPIC contributes to increased precision and accuracy in the prediction of chronological age

Methods

Results

Conclusion