Technical variability across the 450K, EPICv1, and EPICv2 DNA methylation arrays: lessons learned for clinical and longitudinal studies.

Journal: Clinical epigenetics

Volume: 16

Issue: 1

Year of Publication: 2024

Affiliated Institutions:  Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. alussier@mgh.harvard.edu. Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada. SAMRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa. Department of Pediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa. Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. erindunn@purdue.edu.

Abstract summary 

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.

Authors & Co-authors:  Lussier Alexandre A AA Schuurmans Isabel K IK Großbach Anna A Maclsaac Julie J Dever Kristy K Koen Nastassja N Zar Heather J HJ Stein Dan J DJ Kobor Michael S MS Dunn Erin C EC

Study Outcome 

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Statistics
Citations :  Szyf M, McGowan P, Meaney MJ. The social environment and the epigenome. Environ Mol Mutagen. 2008;49(1):46–60.
Authors :  10
Identifiers
Doi : 166
SSN : 1868-7083
Study Population
Male,Female
Mesh Terms
Humans
Other Terms
DNA methylation;Drakenstein Child Health Study;Epigenetics;Illumina arrays;Longitudinal;Reproducibility
Study Design
Longitudinal Study
Study Approach
Country of Study
Publication Country
Germany