Cord blood buffy coat DNA methylation is comparable to whole cord blood methylation

John Dou, Rebecca J. Schmidt, Kelly Benke, Craig Newschaffer, Irva Hertz-Picciotto, Lisa A. Croen, Ana Maria Iosif, Janine M. LaSalle, Daniele Daniele Fallin, Kelly M. Bakulski

Research output: Contribution to journalArticle

Abstract

Cord blood DNA methylation is associated with numerous health outcomes and environmental exposures. Whole cord blood DNA reflects all nucleated blood cell types, while centrifuging whole blood separates red blood cells, generating a white blood cell buffy coat. Both sample types are used in DNA methylation studies. Cell types have unique methylation patterns and processing can impact cell distributions, which may influence comparability. We evaluated differences in cell composition and DNA methylation between cord blood buffy coat and whole cord blood samples. Cord blood DNA methylation was measured with the Infinium EPIC BeadChip (Illumina) in eight individuals, each contributing buffy coat and whole blood samples. We analyzed principal components (PC) of methylation, performed hierarchical clustering, and computed correlations of mean-centered methylation between pairs. We conducted moderated t-tests on single sites and estimated cell composition. DNA methylation PCs were associated with individual (PPC1 = 1.4 × 10−9; PPC2 = 2.9 × 10−5; PPC3 = 3.8 × 10-5; PPC4 = 4.2 × 10-6; PPC5 = 9.9 × 10-13, PPC6 = 1.3 × 10−11) and not with sample type (PPC1-6>0.7). Samples hierarchically clustered by individual. Pearson correlations of mean-centered methylation between paired samples ranged from r = 0.66 to r = 0.87. No individual site significantly differed between buffy coat and whole cord blood when adjusting for multiple comparisons (five sites had unadjusted P<10−5). Estimated cell type proportions did not differ by sample type (P = 0.46), and estimated proportions were highly correlated between paired samples (r = 0.99). Differences in methylation and cell composition between buffy coat and whole cord blood are much lower than inter-individual variation, demonstrating that both sample preparation types can be analytically combined and compared.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalEpigenetics
DOIs
StateAccepted/In press - Feb 1 2018

Fingerprint

Blood Buffy Coat
DNA Methylation
Fetal Blood
Methylation
Glycocalyx
Environmental Exposure
Cluster Analysis
Blood Cells
Leukocytes
Erythrocytes
DNA

Keywords

  • buffy coat
  • cord blood
  • DNA methylation
  • epigenetic epidemiology
  • whole blood

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

Dou, J., Schmidt, R. J., Benke, K., Newschaffer, C., Hertz-Picciotto, I., Croen, L. A., ... Bakulski, K. M. (Accepted/In press). Cord blood buffy coat DNA methylation is comparable to whole cord blood methylation. Epigenetics, 1-9. https://doi.org/10.1080/15592294.2017.1417710

Cord blood buffy coat DNA methylation is comparable to whole cord blood methylation. / Dou, John; Schmidt, Rebecca J.; Benke, Kelly; Newschaffer, Craig; Hertz-Picciotto, Irva; Croen, Lisa A.; Iosif, Ana Maria; LaSalle, Janine M.; Fallin, Daniele Daniele; Bakulski, Kelly M.

In: Epigenetics, 01.02.2018, p. 1-9.

Research output: Contribution to journalArticle

Dou, J, Schmidt, RJ, Benke, K, Newschaffer, C, Hertz-Picciotto, I, Croen, LA, Iosif, AM, LaSalle, JM, Fallin, DD & Bakulski, KM 2018, 'Cord blood buffy coat DNA methylation is comparable to whole cord blood methylation', Epigenetics, pp. 1-9. https://doi.org/10.1080/15592294.2017.1417710
Dou, John ; Schmidt, Rebecca J. ; Benke, Kelly ; Newschaffer, Craig ; Hertz-Picciotto, Irva ; Croen, Lisa A. ; Iosif, Ana Maria ; LaSalle, Janine M. ; Fallin, Daniele Daniele ; Bakulski, Kelly M. / Cord blood buffy coat DNA methylation is comparable to whole cord blood methylation. In: Epigenetics. 2018 ; pp. 1-9.
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