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

Autor: Lussier AA; Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. alussier@mgh.harvard.edu.; Department of Psychiatry, Harvard Medical School, Boston, MA, USA. alussier@mgh.harvard.edu.; Stanley Center for Psychiatric Research, The Broad Institute of Harvard and MIT, Cambridge, MA, USA. alussier@mgh.harvard.edu., Schuurmans IK; Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands., Großbach A; Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.; School of Mathematical and Statistical Sciences, University of Galway, Galway, Ireland.; The SFI Centre for Research Training in Genomics Data Science, Dublin, Ireland., Maclsaac J; Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.; British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.; Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada., Dever K; Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.; British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.; Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada., Koen N; SAMRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa., Zar HJ; Department of Pediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.; South African Medical Research Council (SAMRC) Unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa., Stein DJ; SAMRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa., Kobor MS; Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.; British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.; Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada.; Edwin S.H. Leong Centre for Healthy Aging, University of British Columbia, Vancouver, BC, Canada., Dunn EC; Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. erindunn@purdue.edu.; Department of Psychiatry, Harvard Medical School, Boston, MA, USA. erindunn@purdue.edu.; Stanley Center for Psychiatric Research, The Broad Institute of Harvard and MIT, Cambridge, MA, USA. erindunn@purdue.edu.; Department of Sociology, College of Liberal Arts, Purdue University, West Lafayette, IN, USA. erindunn@purdue.edu.
Jazyk: angličtina
Zdroj: Clinical epigenetics [Clin Epigenetics] 2024 Nov 22; Vol. 16 (1), pp. 166. Date of Electronic Publication: 2024 Nov 22.
DOI: 10.1186/s13148-024-01761-4
Abstrakt: 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.
Competing Interests: Declarations. Ethics approval and consent to participate: Written informed consent was obtained from mothers at enrolment and thereafter annually. The study was approved by the Human Research Ethics Committee of the Faculty of Health Sciences, University of Cape Town, by Stellenbosch University and the Western Cape Provincial Research committee (HREC UCT REF 401/2009; HREC UCT REF 525/2012) [17]. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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