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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\u00a0k 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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>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\u00a0k platform\u00a0and 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\u00a0k data on associations between prenatal paracetamol exposure and cord blood DNAm. A subset of the samples (<jats:italic>n<\/jats:italic>\u2009=\u200917) 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 (<jats:inline-formula><jats:alternatives><jats:tex-math>$$\\stackrel{\\mathrm{-}}{\\text{R}}\\hspace{0.17em}\\approx$$<\/jats:tex-math><mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                    <mml:mrow>\n                      <mml:mover>\n                        <mml:mtext>R<\/mml:mtext>\n                        <mml:mo>-<\/mml:mo>\n                      <\/mml:mover>\n                      <mml:mspace\/>\n                      <mml:mo>\u2248<\/mml:mo>\n                    <\/mml:mrow>\n                  <\/mml:math><\/jats:alternatives><\/jats:inline-formula>\u20090.99), but low per-CpG correlations (<jats:inline-formula><jats:alternatives><jats:tex-math>$$\\stackrel{\\mathrm{-}}{\\text{R}}$$<\/jats:tex-math><mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                    <mml:mover>\n                      <mml:mtext>R<\/mml:mtext>\n                      <mml:mo>-<\/mml:mo>\n                    <\/mml:mover>\n                  <\/mml:math><\/jats:alternatives><\/jats:inline-formula>\u2009\u2248\u20090.24) between the platforms. 1.7% of the CpGs exhibited a mean DNAm difference across platforms &gt;\u20090.1. Furthermore, only 26.7% of the CpGs exhibited a moderate or better cross-platform reliability (intra-class correlation coefficient \u2265\u20090.5).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>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.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13148-022-01299-3","type":"journal-article","created":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T06:03:58Z","timestamp":1656396238000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Low reliability of DNA methylation across Illumina Infinium platforms in cord blood: implications for replication studies and meta-analyses of prenatal exposures"],"prefix":"10.1186","volume":"14","author":[{"given":"Emilie Willoch","family":"Olstad","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hedvig Marie Egeland","family":"Nordeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geir Kjetil","family":"Sandve","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Lyle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina","family":"Gervin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,6,28]]},"reference":[{"key":"1299_CR1","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/nrg3405","volume":"14","author":"J Mill","year":"2013","unstructured":"Mill J, Heijmans BT. 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MoBa is currently regulated by the Norwegian Health Registry Act. All MoBa participants have given their written informed consent to participate in the cohort study. The current study has been approved by REC South East Norway (REC reference: 23136, 2014\/163). All data are de-identified, and the linkage between MoBa and the different health registries was handled by NIPH along with the relevant registries.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"80"}}