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Seven-CpG DNA Methylation Age Determined by Single Nucleotide Primer Extension and Illumina’s Infinium MethylationEPIC Array Provide Highly Comparable Results

DNA methylation age (DNAm age, epigenetic clock) is a novel and promising biomarker of aging. It is calculated from the methylation fraction of specific cytosine phosphate guanine sites (CpG sites) of genomic DNA. Several groups have proposed epigenetic clock algorithms and these differ mostly regar...

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Autores principales: Vetter, Valentin Max, Kalies, Christian Humberto, Sommerer, Yasmine, Bertram, Lars, Demuth, Ilja
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8802213/
https://www.ncbi.nlm.nih.gov/pubmed/35111197
http://dx.doi.org/10.3389/fgene.2021.759357
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author Vetter, Valentin Max
Kalies, Christian Humberto
Sommerer, Yasmine
Bertram, Lars
Demuth, Ilja
author_facet Vetter, Valentin Max
Kalies, Christian Humberto
Sommerer, Yasmine
Bertram, Lars
Demuth, Ilja
author_sort Vetter, Valentin Max
collection PubMed
description DNA methylation age (DNAm age, epigenetic clock) is a novel and promising biomarker of aging. It is calculated from the methylation fraction of specific cytosine phosphate guanine sites (CpG sites) of genomic DNA. Several groups have proposed epigenetic clock algorithms and these differ mostly regarding the number and location of the CpG sites considered and the method used to assess the methylation status. Most epigenetic clocks are based on a large number of CpGs, e.g. as measured by DNAm microarrays. We have recently evaluated an epigenetic clock based on the methylation fraction of seven CpGs that were determined by methylation-sensitive single nucleotide primer extension (MS-SNuPE). This method is more cost-effective when compared to array-based technologies as only a few CpGs need to be examined. However, there is only little data on the correspondence in epigenetic age estimation using the 7-CpG clock and other algorithms. To bridge this gap, in this study we measured the 7-CpG DNAm age using two methods, via MS-SNuPE and via the MethylationEPIC array, in a sample of 1,058 participants of the Berlin Aging Study II (BASE-II), assessed as part of the GendAge study. On average, participants were 75.6 years old (SD: 3.7, age range: 64.9–90.0, 52.6% female). Agreement between methods was assessed by Bland-Altman plots. DNAm age was highly correlated between methods (Pearson’s r = 0.9) and Bland-Altman plots showed a difference of 3.1 years. DNAm age by the 7-CpG formula was 71.2 years (SD: 6.9 years, SNuPE) and 68.1 years (SD: 6.4 years, EPIC array). The mean of difference in methylation fraction between methods for the seven individual CpG sites was between 0.7 and 13 percent. To allow direct conversion of DNAm age obtained from both methods we developed an adjustment formula with a randomly selected training set of 529 participants using linear regression. After conversion of the Illumina data in a second and independent validation set, the adjusted DNAm age was 71.44 years (SD: 6.1 years, n = 529). In summary, we found the results of DNAm clocks to be highly comparable. Furthermore, we developed an adjustment formula that allows for direct conversion of DNAm age estimates between methods and enables one singular clock to be used in studies that employ either the Illumina or the SNuPE method.
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spelling pubmed-88022132022-02-01 Seven-CpG DNA Methylation Age Determined by Single Nucleotide Primer Extension and Illumina’s Infinium MethylationEPIC Array Provide Highly Comparable Results Vetter, Valentin Max Kalies, Christian Humberto Sommerer, Yasmine Bertram, Lars Demuth, Ilja Front Genet Genetics DNA methylation age (DNAm age, epigenetic clock) is a novel and promising biomarker of aging. It is calculated from the methylation fraction of specific cytosine phosphate guanine sites (CpG sites) of genomic DNA. Several groups have proposed epigenetic clock algorithms and these differ mostly regarding the number and location of the CpG sites considered and the method used to assess the methylation status. Most epigenetic clocks are based on a large number of CpGs, e.g. as measured by DNAm microarrays. We have recently evaluated an epigenetic clock based on the methylation fraction of seven CpGs that were determined by methylation-sensitive single nucleotide primer extension (MS-SNuPE). This method is more cost-effective when compared to array-based technologies as only a few CpGs need to be examined. However, there is only little data on the correspondence in epigenetic age estimation using the 7-CpG clock and other algorithms. To bridge this gap, in this study we measured the 7-CpG DNAm age using two methods, via MS-SNuPE and via the MethylationEPIC array, in a sample of 1,058 participants of the Berlin Aging Study II (BASE-II), assessed as part of the GendAge study. On average, participants were 75.6 years old (SD: 3.7, age range: 64.9–90.0, 52.6% female). Agreement between methods was assessed by Bland-Altman plots. DNAm age was highly correlated between methods (Pearson’s r = 0.9) and Bland-Altman plots showed a difference of 3.1 years. DNAm age by the 7-CpG formula was 71.2 years (SD: 6.9 years, SNuPE) and 68.1 years (SD: 6.4 years, EPIC array). The mean of difference in methylation fraction between methods for the seven individual CpG sites was between 0.7 and 13 percent. To allow direct conversion of DNAm age obtained from both methods we developed an adjustment formula with a randomly selected training set of 529 participants using linear regression. After conversion of the Illumina data in a second and independent validation set, the adjusted DNAm age was 71.44 years (SD: 6.1 years, n = 529). In summary, we found the results of DNAm clocks to be highly comparable. Furthermore, we developed an adjustment formula that allows for direct conversion of DNAm age estimates between methods and enables one singular clock to be used in studies that employ either the Illumina or the SNuPE method. Frontiers Media S.A. 2022-01-17 /pmc/articles/PMC8802213/ /pubmed/35111197 http://dx.doi.org/10.3389/fgene.2021.759357 Text en Copyright © 2022 Vetter, Kalies, Sommerer, Bertram and Demuth. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Vetter, Valentin Max
Kalies, Christian Humberto
Sommerer, Yasmine
Bertram, Lars
Demuth, Ilja
Seven-CpG DNA Methylation Age Determined by Single Nucleotide Primer Extension and Illumina’s Infinium MethylationEPIC Array Provide Highly Comparable Results
title Seven-CpG DNA Methylation Age Determined by Single Nucleotide Primer Extension and Illumina’s Infinium MethylationEPIC Array Provide Highly Comparable Results
title_full Seven-CpG DNA Methylation Age Determined by Single Nucleotide Primer Extension and Illumina’s Infinium MethylationEPIC Array Provide Highly Comparable Results
title_fullStr Seven-CpG DNA Methylation Age Determined by Single Nucleotide Primer Extension and Illumina’s Infinium MethylationEPIC Array Provide Highly Comparable Results
title_full_unstemmed Seven-CpG DNA Methylation Age Determined by Single Nucleotide Primer Extension and Illumina’s Infinium MethylationEPIC Array Provide Highly Comparable Results
title_short Seven-CpG DNA Methylation Age Determined by Single Nucleotide Primer Extension and Illumina’s Infinium MethylationEPIC Array Provide Highly Comparable Results
title_sort seven-cpg dna methylation age determined by single nucleotide primer extension and illumina’s infinium methylationepic array provide highly comparable results
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8802213/
https://www.ncbi.nlm.nih.gov/pubmed/35111197
http://dx.doi.org/10.3389/fgene.2021.759357
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