Cell type specific DNA methylation in cord blood: A 450K-reference data set and cell count-based validation of estimated cell type composition

Kristina Gervin, Christian Magnus Page, Hans Christian D. Aass, Michelle A. Jansen, Heidi Elisabeth Fjeldstad, Bettina Kulle Andreassen, Liesbeth Duijts, Joyce B. van Meurs, Menno C. van Zelm, Vincent W. Jaddoe, Hedvig Nordeng, Gunn Peggy Knudsen, Per Magnus, Wenche Nystad, Anne Cathrine Staff, Janine F. Felix, Robert Lyle

Research output: Contribution to journalArticleResearchpeer-review

42 Citations (Scopus)

Abstract

Epigenome-wide association studies of prenatal exposure to different environmental factors are becoming increasingly common. These studies are usually performed in umbilical cord blood. Since blood comprises multiple cell types with specific DNA methylation patterns, confounding caused by cellular heterogeneity is a major concern. This can be adjusted for using reference data consisting of DNA methylation signatures in cell types isolated from blood. However, the most commonly used reference data set is based on blood samples from adult males and is not representative of the cell type composition in neonatal cord blood. The aim of this study was to generate a reference data set from cord blood to enable correct adjustment of the cell type composition in samples collected at birth. The purity of the isolated cell types was very high for all samples (>97.1%), and clustering analyses showed distinct grouping of the cell types according to hematopoietic lineage. We explored whether this cord blood and the adult peripheral blood reference data sets impact the estimation of cell type composition in cord blood samples from an independent birth cohort (MoBa, n = 1092). This revealed significant differences for all cell types. Importantly, comparison of the cell type estimates against matched cell counts both in the cord blood reference samples (n = 11) and in another independent birth cohort (Generation R, n = 195), demonstrated moderate to high correlation of the data. This is the first cord blood reference data set with a comprehensive examination of the downstream application of the data through validation of estimated cell types against matched cell counts.

Original languageEnglish
Pages (from-to)690-698
Number of pages9
JournalEpigenetics
Volume11
Issue number9
DOIs
Publication statusPublished - 1 Sep 2016

Keywords

  • Cellular heterogeneity
  • cord blood
  • DNA methylation
  • EWAS
  • reference data set

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