Sammendrag
Background: There is an increasing interest in the role of epigenetics in epidemiology, but the emerging research
feld faces several critical biological and technical challenges. In particular, recent studies have shown poor correlation of measured DNA methylation (DNAm) levels within and across Illumina Infnium platforms in various tissues. In this study, we have investigated concordance between 450 k and EPIC Infnium platforms in cord blood. We could not
replicate our previous fndings on the association of prenatal paracetamol exposure with cord blood DNAm, which
prompted an investigation of cross-platform DNAm diferences.
Results: This study is based on two DNAm data sets from cord blood samples selected from the Norwegian Mother,
Father and Child Cohort Study (MoBa). DNAm of one data set was measured using the 450 k platform and the other
data set was measured using the EPIC platform. Initial analyses of the EPIC data could not replicate any of our previous signifcant fndings in the 450 k data on associations between prenatal paracetamol exposure and cord blood DNAm.
A subset of the samples (n=17) was included in both data sets, which enabled analyses of technical sources potentially contributing to the negative replication. Analyses of these 17 samples with repeated measurements revealed high per-sample correlations (−R ≈0.99), but low per-CpG correlations (−R≈0.24) between the platforms. 1.7% of the CpGs exhibited a mean DNAm diference across platforms >0.1. Furthermore, only 26.7% of the CpGs exhibited a
moderate or better cross-platform reliability (intra-class correlation coefcient ≥0.5).
Conclusion: The observations of low cross-platform probe correlation and reliability corroborate previous reports in
other tissues. Our study cannot determine the origin of the diferences between platforms. Nevertheless, it emulates
the setting in studies using data from multiple Infnium platforms, often analysed several years apart. Therefore, the
fndings may have important implications for future epigenome-wide association studies (EWASs), in replication,
meta-analyses and longitudinal studies. Cognisance and transparency of the challenges related to cross-platform
studies may enhance the interpretation, replicability and validity of EWAS results both in cord blood and other tissues, ultimately improving the clinical relevance of epigenetic epidemiology.
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