Blood transcriptomic associations of epigenetic age in adolescents

Epigenetic aging in early life remains poorly characterized, and patterns of gene expression can provide biologically meaningful insights. Blood DNA methylation was measured using the Illumina EPICv1.0 array and RNA sequencing was performed in blood in 174 adolescent participants (age range: 14–15 y...

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Main Authors: Dennis Khodasevich, Anne K Bozack, Saher Daredia, Julianna Deardorff, Kim G Harley, Brenda Eskenazi, Weihong Guo, Nina Holland, Andres Cardenas
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Epigenetics
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Online Access:https://www.tandfonline.com/doi/10.1080/15592294.2025.2503824
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author Dennis Khodasevich
Anne K Bozack
Saher Daredia
Julianna Deardorff
Kim G Harley
Brenda Eskenazi
Weihong Guo
Nina Holland
Andres Cardenas
author_facet Dennis Khodasevich
Anne K Bozack
Saher Daredia
Julianna Deardorff
Kim G Harley
Brenda Eskenazi
Weihong Guo
Nina Holland
Andres Cardenas
author_sort Dennis Khodasevich
collection DOAJ
description Epigenetic aging in early life remains poorly characterized, and patterns of gene expression can provide biologically meaningful insights. Blood DNA methylation was measured using the Illumina EPICv1.0 array and RNA sequencing was performed in blood in 174 adolescent participants (age range: 14–15 years) from the CHAMACOS cohort. Thirteen widely used epigenetic clocks were calculated, and their associations with transcriptome-wide RNA expression were tested using the limma-voom pipeline. We found evidence for substantial shared associations with RNA expression between different epigenetic clocks, including differential expression of MYO6 and ZBTB38 across five clocks. The epiTOC2, principal component (PC) PhenoAge, Hannum, PedBE and PC Hannum clocks were associated with differential expression of the highest number of RNAs, exhibiting associations with 22, 8, 5, 3, and 2 transcripts respectively. Generally, biological clocks were associated with differential expression of more genes than chronological clocks, and PC clocks were associated with differential expression of more genes relative to their CpG-trained counterparts. A total of 17 associations in our study were replicated in an independent adult sample (age range: 40–54 years). Our findings support the biological relevance of epigenetic clocks in adolescents and provide direction for selection of epigenetic ageing biomarkers in adolescent research.
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spelling doaj-art-cccfb58a142e4fe680376b9fb3447e482025-08-20T02:31:46ZengTaylor & Francis GroupEpigenetics1559-22941559-23082025-12-0120110.1080/15592294.2025.2503824Blood transcriptomic associations of epigenetic age in adolescentsDennis Khodasevich0Anne K Bozack1Saher Daredia2Julianna Deardorff3Kim G Harley4Brenda Eskenazi5Weihong Guo6Nina Holland7Andres Cardenas8Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, USADepartment of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, USADivision of Epidemiology, Berkeley Public Health, University of California, Berkeley, CA, USACenter for Environmental Research and Community Health (CERCH), Berkeley Public Health, University of California, Berkeley, CA, USACenter for Environmental Research and Community Health (CERCH), Berkeley Public Health, University of California, Berkeley, CA, USACenter for Environmental Research and Community Health (CERCH), Berkeley Public Health, University of California, Berkeley, CA, USACenter for Environmental Research and Community Health (CERCH), Berkeley Public Health, University of California, Berkeley, CA, USACenter for Environmental Research and Community Health (CERCH), Berkeley Public Health, University of California, Berkeley, CA, USADepartment of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, USAEpigenetic aging in early life remains poorly characterized, and patterns of gene expression can provide biologically meaningful insights. Blood DNA methylation was measured using the Illumina EPICv1.0 array and RNA sequencing was performed in blood in 174 adolescent participants (age range: 14–15 years) from the CHAMACOS cohort. Thirteen widely used epigenetic clocks were calculated, and their associations with transcriptome-wide RNA expression were tested using the limma-voom pipeline. We found evidence for substantial shared associations with RNA expression between different epigenetic clocks, including differential expression of MYO6 and ZBTB38 across five clocks. The epiTOC2, principal component (PC) PhenoAge, Hannum, PedBE and PC Hannum clocks were associated with differential expression of the highest number of RNAs, exhibiting associations with 22, 8, 5, 3, and 2 transcripts respectively. Generally, biological clocks were associated with differential expression of more genes than chronological clocks, and PC clocks were associated with differential expression of more genes relative to their CpG-trained counterparts. A total of 17 associations in our study were replicated in an independent adult sample (age range: 40–54 years). Our findings support the biological relevance of epigenetic clocks in adolescents and provide direction for selection of epigenetic ageing biomarkers in adolescent research.https://www.tandfonline.com/doi/10.1080/15592294.2025.2503824Epigeneticstranscriptomeadolescentepigenetic aging
spellingShingle Dennis Khodasevich
Anne K Bozack
Saher Daredia
Julianna Deardorff
Kim G Harley
Brenda Eskenazi
Weihong Guo
Nina Holland
Andres Cardenas
Blood transcriptomic associations of epigenetic age in adolescents
Epigenetics
Epigenetics
transcriptome
adolescent
epigenetic aging
title Blood transcriptomic associations of epigenetic age in adolescents
title_full Blood transcriptomic associations of epigenetic age in adolescents
title_fullStr Blood transcriptomic associations of epigenetic age in adolescents
title_full_unstemmed Blood transcriptomic associations of epigenetic age in adolescents
title_short Blood transcriptomic associations of epigenetic age in adolescents
title_sort blood transcriptomic associations of epigenetic age in adolescents
topic Epigenetics
transcriptome
adolescent
epigenetic aging
url https://www.tandfonline.com/doi/10.1080/15592294.2025.2503824
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