Low reliability of DNA methylation across Illumina Infinium platforms in cord blood: implications for replication studies and meta-analyses of prenatal exposures

Background There is an increasing interest in the role of epigenetics in epidemiology, but the emerging research field 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 Infinium platforms in various tissues. In this study, we have investigated concordance between 450 k and EPIC Infinium platforms in cord blood. We could not replicate our previous findings on the association of prenatal paracetamol exposure with cord blood DNAm, which prompted an investigation of cross-platform DNAm differences. 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 significant findings 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