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 Existing epigenetic clocks are based on CpGs from the Illumina HumanMethylation450 BeadChip (450 K) which has now been replaced by the latest p...

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Main Authors: Yunsung Lee, Kristine L. Haftorn, William R. P. Denault, Haakon E. Nustad, Christian M. Page, Robert Lyle, Sindre Lee-Ødegård, Gunn-Helen Moen, Rashmi B. Prasad, Leif C. Groop, Line Sletner, Christine Sommer, Maria C. Magnus, Håkon K. Gjessing, Jennifer R. Harris, Per Magnus, Siri E. Håberg, Astanand Jugessur, Jon Bohlin
Format: Article
Language:English
Published: BMC 2020-10-01
Series:BMC Genomics
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Online Access:http://link.springer.com/article/10.1186/s12864-020-07168-8
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author Yunsung Lee
Kristine L. Haftorn
William R. P. Denault
Haakon E. Nustad
Christian M. Page
Robert Lyle
Sindre Lee-Ødegård
Gunn-Helen Moen
Rashmi B. Prasad
Leif C. Groop
Line Sletner
Christine Sommer
Maria C. Magnus
Håkon K. Gjessing
Jennifer R. Harris
Per Magnus
Siri E. Håberg
Astanand Jugessur
Jon Bohlin
author_facet Yunsung Lee
Kristine L. Haftorn
William R. P. Denault
Haakon E. Nustad
Christian M. Page
Robert Lyle
Sindre Lee-Ødegård
Gunn-Helen Moen
Rashmi B. Prasad
Leif C. Groop
Line Sletner
Christine Sommer
Maria C. Magnus
Håkon K. Gjessing
Jennifer R. Harris
Per Magnus
Siri E. Håberg
Astanand Jugessur
Jon Bohlin
author_sort Yunsung Lee
collection DOAJ
description 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 Existing epigenetic clocks are based on CpGs from the Illumina HumanMethylation450 BeadChip (450 K) which has now been replaced by the latest platform, Illumina MethylationEPIC BeadChip (EPIC).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.
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spelling doaj.art-0615d625d2304aafb5a4fea374fd29382022-12-22T00:17:09ZengBMCBMC Genomics1471-21642020-10-0121111310.1186/s12864-020-07168-8Blood-based epigenetic estimators of chronological age in human adults using DNA methylation data from the Illumina MethylationEPIC arrayYunsung Lee0Kristine L. Haftorn1William R. P. Denault2Haakon E. Nustad3Christian M. Page4Robert Lyle5Sindre Lee-Ødegård6Gunn-Helen Moen7Rashmi B. Prasad8Leif C. Groop9Line Sletner10Christine Sommer11Maria C. Magnus12Håkon K. Gjessing13Jennifer R. Harris14Per Magnus15Siri E. Håberg16Astanand Jugessur17Jon Bohlin18Department of Genetics and Bioinformatics, Norwegian Institute of Public HealthDepartment of Genetics and Bioinformatics, Norwegian Institute of Public HealthDepartment of Genetics and Bioinformatics, Norwegian Institute of Public HealthCentre for Fertility and Health, Norwegian Institute of Public HealthCentre for Fertility and Health, Norwegian Institute of Public HealthCentre for Fertility and Health, Norwegian Institute of Public HealthDepartment of Internal Medicine, Akershus University HospitalInstitute of Clinical Medicine, Faculty of Medicine, University of OsloDepartment of Clinical Sciences, Clinical Research Centre, Lund UniversityDepartment of Clinical Sciences, Clinical Research Centre, Lund UniversityDepartment of Pediatric and Adolescents Medicine, Akershus University HospitalDepartment of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University HospitalCentre for Fertility and Health, Norwegian Institute of Public HealthCentre for Fertility and Health, Norwegian Institute of Public HealthDepartment of Genetics and Bioinformatics, Norwegian Institute of Public HealthCentre for Fertility and Health, Norwegian Institute of Public HealthCentre for Fertility and Health, Norwegian Institute of Public HealthDepartment of Genetics and Bioinformatics, Norwegian Institute of Public HealthCentre for Fertility and Health, Norwegian Institute of Public HealthAbstract 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.http://link.springer.com/article/10.1186/s12864-020-07168-8DNA methylationEpigenetic ageChronological ageIllumina MethylationEPIC BeadChipMoBa
spellingShingle Yunsung Lee
Kristine L. Haftorn
William R. P. Denault
Haakon E. Nustad
Christian M. Page
Robert Lyle
Sindre Lee-Ødegård
Gunn-Helen Moen
Rashmi B. Prasad
Leif C. Groop
Line Sletner
Christine Sommer
Maria C. Magnus
Håkon K. Gjessing
Jennifer R. Harris
Per Magnus
Siri E. Håberg
Astanand Jugessur
Jon Bohlin
Blood-based epigenetic estimators of chronological age in human adults using DNA methylation data from the Illumina MethylationEPIC array
BMC Genomics
DNA methylation
Epigenetic age
Chronological age
Illumina MethylationEPIC BeadChip
MoBa
title Blood-based epigenetic estimators of chronological age in human adults using DNA methylation data from the Illumina MethylationEPIC array
title_full Blood-based epigenetic estimators of chronological age in human adults using DNA methylation data from the Illumina MethylationEPIC array
title_fullStr Blood-based epigenetic estimators of chronological age in human adults using DNA methylation data from the Illumina MethylationEPIC array
title_full_unstemmed Blood-based epigenetic estimators of chronological age in human adults using DNA methylation data from the Illumina MethylationEPIC array
title_short Blood-based epigenetic estimators of chronological age in human adults using DNA methylation data from the Illumina MethylationEPIC array
title_sort blood based epigenetic estimators of chronological age in human adults using dna methylation data from the illumina methylationepic array
topic DNA methylation
Epigenetic age
Chronological age
Illumina MethylationEPIC BeadChip
MoBa
url http://link.springer.com/article/10.1186/s12864-020-07168-8
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