Technical variability across the 450K, EPICv1, and EPICv2 DNA methylation arrays: lessons learned for clinical and longitudinal studies
Abstract DNA methylation (DNAm) is the most commonly measured epigenetic mechanism in human populations, with most studies using Illumina arrays to assess DNAm levels. In 2023, Illumina updated their DNAm arrays to the EPIC version 2 (EPICv2), building on prior iterations, namely the EPIC version 1...
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BMC
2024-11-01
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| Series: | Clinical Epigenetics |
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| Online Access: | https://doi.org/10.1186/s13148-024-01761-4 |
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| author | Alexandre A. Lussier Isabel K. Schuurmans Anna Großbach Julie Maclsaac Kristy Dever Nastassja Koen Heather J. Zar Dan J. Stein Michael S. Kobor Erin C. Dunn |
| author_facet | Alexandre A. Lussier Isabel K. Schuurmans Anna Großbach Julie Maclsaac Kristy Dever Nastassja Koen Heather J. Zar Dan J. Stein Michael S. Kobor Erin C. Dunn |
| author_sort | Alexandre A. Lussier |
| collection | DOAJ |
| description | Abstract DNA methylation (DNAm) is the most commonly measured epigenetic mechanism in human populations, with most studies using Illumina arrays to assess DNAm levels. In 2023, Illumina updated their DNAm arrays to the EPIC version 2 (EPICv2), building on prior iterations, namely the EPIC version 1 (EPICv1) and 450K arrays. Whether DNAm measurements are stable across these three generations of arrays has yet not been investigated, limiting the ability of researchers—especially those with longitudinal data—to compare and replicate results across arrays. Here, we present results from a study of 30 child participants (15 male; 15 female) from the Drakenstein Child Health Study, who had DNAm measured on all three of the latest arrays: 450K, EPICv1, and EPICv2. Using these data, we created an annotation of probe quality across arrays, which includes the intraclass correlations, interquartile ranges, correlations, and array bias (i.e., the extent to which DNAm levels were explained by array type) of all CpGs. We also present results from an analysis of sex differences, where we found that CpGs with lower replicability across arrays had higher array-based variance, suggesting this variance metric help guide replication efforts. We also showed that epigenetic age estimates across arrays were more stable when using the principal component versions of epigenetic clocks. Ultimately, this collection of results provides a framework for investigating the replicability and longitudinal stability of epigenetic changes across multiple versions of Illumina DNAm arrays. |
| format | Article |
| id | doaj-art-45bc3d1658e04f92acaf7744d5dae6f1 |
| institution | Kabale University |
| issn | 1868-7083 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj-art-45bc3d1658e04f92acaf7744d5dae6f12024-11-24T12:31:08ZengBMCClinical Epigenetics1868-70832024-11-0116111210.1186/s13148-024-01761-4Technical variability across the 450K, EPICv1, and EPICv2 DNA methylation arrays: lessons learned for clinical and longitudinal studiesAlexandre A. Lussier0Isabel K. Schuurmans1Anna Großbach2Julie Maclsaac3Kristy Dever4Nastassja Koen5Heather J. Zar6Dan J. Stein7Michael S. Kobor8Erin C. Dunn9Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General HospitalDepartment of Child and Adolescent Psychiatry/Psychology, Erasmus MC University Medical Center RotterdamPsychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General HospitalDepartment of Medical Genetics, Faculty of Medicine, University of British ColumbiaDepartment of Medical Genetics, Faculty of Medicine, University of British ColumbiaSAMRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape TownDepartment of Pediatrics and Child Health, Red Cross War Memorial Children’s Hospital, University of Cape TownSAMRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape TownDepartment of Medical Genetics, Faculty of Medicine, University of British ColumbiaPsychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General HospitalAbstract DNA methylation (DNAm) is the most commonly measured epigenetic mechanism in human populations, with most studies using Illumina arrays to assess DNAm levels. In 2023, Illumina updated their DNAm arrays to the EPIC version 2 (EPICv2), building on prior iterations, namely the EPIC version 1 (EPICv1) and 450K arrays. Whether DNAm measurements are stable across these three generations of arrays has yet not been investigated, limiting the ability of researchers—especially those with longitudinal data—to compare and replicate results across arrays. Here, we present results from a study of 30 child participants (15 male; 15 female) from the Drakenstein Child Health Study, who had DNAm measured on all three of the latest arrays: 450K, EPICv1, and EPICv2. Using these data, we created an annotation of probe quality across arrays, which includes the intraclass correlations, interquartile ranges, correlations, and array bias (i.e., the extent to which DNAm levels were explained by array type) of all CpGs. We also present results from an analysis of sex differences, where we found that CpGs with lower replicability across arrays had higher array-based variance, suggesting this variance metric help guide replication efforts. We also showed that epigenetic age estimates across arrays were more stable when using the principal component versions of epigenetic clocks. Ultimately, this collection of results provides a framework for investigating the replicability and longitudinal stability of epigenetic changes across multiple versions of Illumina DNAm arrays.https://doi.org/10.1186/s13148-024-01761-4EpigeneticsDrakenstein Child Health StudyDNA methylationIllumina arraysLongitudinalReproducibility |
| spellingShingle | Alexandre A. Lussier Isabel K. Schuurmans Anna Großbach Julie Maclsaac Kristy Dever Nastassja Koen Heather J. Zar Dan J. Stein Michael S. Kobor Erin C. Dunn Technical variability across the 450K, EPICv1, and EPICv2 DNA methylation arrays: lessons learned for clinical and longitudinal studies Clinical Epigenetics Epigenetics Drakenstein Child Health Study DNA methylation Illumina arrays Longitudinal Reproducibility |
| title | Technical variability across the 450K, EPICv1, and EPICv2 DNA methylation arrays: lessons learned for clinical and longitudinal studies |
| title_full | Technical variability across the 450K, EPICv1, and EPICv2 DNA methylation arrays: lessons learned for clinical and longitudinal studies |
| title_fullStr | Technical variability across the 450K, EPICv1, and EPICv2 DNA methylation arrays: lessons learned for clinical and longitudinal studies |
| title_full_unstemmed | Technical variability across the 450K, EPICv1, and EPICv2 DNA methylation arrays: lessons learned for clinical and longitudinal studies |
| title_short | Technical variability across the 450K, EPICv1, and EPICv2 DNA methylation arrays: lessons learned for clinical and longitudinal studies |
| title_sort | technical variability across the 450k epicv1 and epicv2 dna methylation arrays lessons learned for clinical and longitudinal studies |
| topic | Epigenetics Drakenstein Child Health Study DNA methylation Illumina arrays Longitudinal Reproducibility |
| url | https://doi.org/10.1186/s13148-024-01761-4 |
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