Cristin-resultat-ID: 2044459
Sist endret: 17. februar 2023, 15:45
NVI-rapporteringsår: 2022
Resultat
Vitenskapelig artikkel
2022

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

Bidragsytere:
  • Emilie Willoch Olstad
  • Hedvig Marie Egeland Nordeng
  • Geir Kjetil Ferkingstad Sandve
  • Robert Lyle og
  • Kristina Gervin

Tidsskrift

Clinical Epigenetics
ISSN 1868-7075
e-ISSN 1868-7083
NVI-nivå 1

Om resultatet

Vitenskapelig artikkel
Publiseringsår: 2022
Volum: 14
Hefte: 1
Artikkelnummer: 80
Open Access

Importkilder

Scopus-ID: 2-s2.0-85132971511

Beskrivelse Beskrivelse

Tittel

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

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.

Bidragsytere

Emilie Willoch Olstad

  • Tilknyttet:
    Forfatter
    ved Seksjon for galenisk farmasi og samfunns ved Universitetet i Oslo
Aktiv cristin-person

Hedvig Marie Egeland Nordeng

  • Tilknyttet:
    Forfatter
    ved Avdeling for barns helse og utvikling ved Folkehelseinstituttet
  • Tilknyttet:
    Forfatter
    ved Seksjon for galenisk farmasi og samfunns ved Universitetet i Oslo

Geir Kjetil Ferkingstad Sandve

  • Tilknyttet:
    Forfatter
    ved Vitenskapelige beregninger og maskinlæring ved Universitetet i Oslo

Robert Lyle

  • Tilknyttet:
    Forfatter
    ved Avdeling for medisinsk genetikk ved Universitetet i Oslo
  • Tilknyttet:
    Forfatter
    ved Senter for fruktbarhet og helse ved Folkehelseinstituttet
  • Tilknyttet:
    Forfatter
    ved Avdeling for medisinsk genetikk ved Oslo universitetssykehus HF

Kristina Gervin

  • Tilknyttet:
    Forfatter
    ved Seksjon for galenisk farmasi og samfunns ved Universitetet i Oslo
  • Tilknyttet:
    Forfatter
    ved Avdeling for forskning og utvikling, Nevroklinikken ved Oslo universitetssykehus HF
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