Accounting for differences between Infinium MethylationEPIC v2 and v1 in DNA methylation-based tools

Area of Science:

• Genomics
• Epigenetics
• Biotechnology

Background:

• The Illumina MethylationEPIC v2.0 (EPICv2) array succeeds EPICv1, retaining most probes and adding new ones.
• Investigating concordance between EPICv1 and EPICv2 is essential for DNA methylation studies.

Purpose of the Study:

• To assess the concordance between Illumina MethylationEPIC v1.0 (EPICv1) and EPICv2 arrays.
• To evaluate the impact of EPIC version on DNA methylation variation and estimates.

Main Methods:

• DNA methylation profiling was performed on matched blood samples from four adult cohorts using both EPICv1 and EPICv2 arrays.
• Concordance and variation analyses were conducted, considering factors like sample relatedness and cell-type composition.

Main Results:

• High array-level concordance was observed between EPICv1 and EPICv2, with variable agreement at the individual probe level.
• EPIC version significantly contributed to DNA methylation variation, though less than sample relatedness or cell-type composition.
• Modest but significant differences in DNA methylation estimates were found between the two versions, regardless of preprocessing methods.

Conclusions:

• Differences between EPICv1 and EPICv2 arrays can influence DNA methylation estimates.
• Adjusting for EPIC version or analyzing data separately for each version can resolve discordances.
• Accounting for EPIC version is critical for harmonizing data in meta-analyses and longitudinal studies.