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• W4283658697 abstract "Abstract 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 ( $$stackrel{mathrm{-}}{text{R}}hspace{0.17em}approx$$ <mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML> <mml:mrow> <mml:mover> <mml:mtext>R</mml:mtext> <mml:mo>-</mml:mo> </mml:mover> <mml:mspace /> <mml:mo>≈</mml:mo> </mml:mrow> </mml:math> 0.99), but low per-CpG correlations ( $$stackrel{mathrm{-}}{text{R}}$$ <mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML> <mml:mover> <mml:mtext>R</mml:mtext> <mml:mo>-</mml:mo> </mml:mover> </mml:math> ≈ 0.24) between the platforms. 1.7% of the CpGs exhibited a mean DNAm difference across platforms > 0.1. Furthermore, only 26.7% of the CpGs exhibited a moderate or better cross-platform reliability (intra-class correlation coefficient ≥ 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 differences between platforms. Nevertheless, it emulates the setting in studies using data from multiple Infinium platforms, often analysed several years apart. Therefore, the findings 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." @default.
• W4283658697 created "2022-06-29" @default.
• W4283658697 creator A5021639883 @default.
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• W4283658697 creator A5090146676 @default.
• W4283658697 date "2022-06-28" @default.
• W4283658697 modified "2023-10-18" @default.
• W4283658697 title "Low reliability of DNA methylation across Illumina Infinium platforms in cord blood: implications for replication studies and meta-analyses of prenatal exposures" @default.
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• W4283658697 doi "https://doi.org/10.1186/s13148-022-01299-3" @default.
• W4283658697 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35765087" @default.
• W4283658697 hasPublicationYear "2022" @default.
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