Beryl C. Zhuang, Marcia Smiti Jude, Chaini Konwar, Natan Yusupov, Calen P. Ryan, Hannah-Ruth Engelbrecht, Joanne Whitehead, Alexandra A. Halberstam, Julia L. Macisaac, Kristy Dever, Toan Khanh Tran, Kim Korinek, Zachary Zimmer, Nanette R. Lee, Thomas W. McDade, Christopher W. Kuzawa, Kim M. Huffman, Daniel W. Belsky, Elisabeth B. Binder, Darina Czamara, Keegan Korthauer, Michael S. Kobor
The recently launched Illumina Infinium MethylationEPIC v2.0 (EPICv2), successor of MethylationEPIC v1.0 (EPICv1), retains most of the probes in EPICv1, while expanding coverage of regulatory elements. The concordance between the two EPIC versions in DNA methylation–based tools has not yet been investigated. To address this, DNA methylation was profiled on both versions using matched blood samples across four cohorts spanning early to late adulthood. High concordance between versions at the array level but variable agreement at the individual probe level was noted. A significant contribution of the EPIC version to DNA methylation variation was observed, though it was to a smaller extent compared with sample relatedness and cell-type composition. Modest but significant differences in DNA methylation–based estimates between versions were observed, irrespective of the data preprocessing method used. Adjustments for EPIC version or calculation of estimates separately for each version largely mitigated these version-specific discordances. This work emphasizes the importance of accounting for EPIC version differences in research scenarios, especially in meta-analyses and longitudinal studies that require data harmonization across versions. © 2025 Zhuang et al.
Edwin S. H. Leong Centre for Healthy Aging, Faculty of Medicine, University of British Columbia, Vancouver, Canada; Centre for Molecular Medicine and Therapeutics and Department of Medical Genetics, University of British Columbia, Vancouver, Canada; British Columbia Children’s Hospital Research Institute, Vancouver, Canada; Department Genes and Environment, Max Planck Institute of Psychiatry, Munich, Germany; International Max Planck Research School for Translational Psychiatry, Munich, Germany; Robert N. Butler Columbia Aging Center, Mailman School of Public Health, Columbia University, New York, NY, United States; Harvard Medical School/MIT Institute of Technology MD-PhD Program, Boston, MA, United States; Family Medicine Department, Hanoi Medical University, Hanoi, Viet Nam; Department of Sociology, University of Utah, Salt Lake City, UT, United States; Department of Family Studies and Gerontology, Mount Saint Vincent University, Halifax, Canada; Canada Research Chair, Global Aging and Community Initiative, Halifax, Canada; USC-Office of Population Studies Foundation, Inc, University of San Carlos, Cebu City, Philippines; Department of Anthropology, Northwestern University, Evanston, IL, United States; Program in Child and Brain Development, Canadian Institute for Advanced Research, Toronto, Canada; Department of Anthropology and Institute for Policy Research, Northwestern University, Evanston, IL, United States; Duke University School of Medicine, Durham, NC, United States; Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, United States; Department of Statistics, Faculty of Science, University of British Columbia, Vancouver, Canada
