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The tissue-specific aspect of genome-wide DNA methylation in newborn and placental tissues: implications for epigenetic epidemiologic studies

Published online by Cambridge University Press:  24 April 2020

Emilie M. Herzog ,
Alex J. Eggink ,
Sten P. Willemsen ,
Roderick C. Slieker ,
Janine F. Felix ,
Andrew P. Stubbs ,
Peter J. van der Spek ,
Joyce B. J. van Meurs ,
Bastiaan T. Heijmans  and
Régine P. M. Steegers-Theunissen Open the ORCID record for Régine P. M. Steegers-Theunissen [Opens in a new window]
Emilie M. Herzog
Affiliation:
Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CARotterdam, The Netherlands
Alex J. Eggink
Affiliation:
Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CARotterdam, The Netherlands
Sten P. Willemsen
Affiliation:
Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CARotterdam, The Netherlands Department of Biostatistics, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CARotterdam, The Netherlands
Roderick C. Slieker
Affiliation:
Department of Molecular Epidemiology, Leiden University Medical Centre, Postbus 9600, 2300 RCLeiden, The Netherlands
Janine F. Felix
Affiliation:
Department of Epidemiology, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CARotterdam, The Netherlands Generation R Study Group, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CARotterdam, The Netherlands Department of Paediatrics, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CARotterdam, The Netherlands
Andrew P. Stubbs
Affiliation:
Department of Bioinformatics, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CARotterdam, The Netherlands
Peter J. van der Spek
Affiliation:
Department of Bioinformatics, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CARotterdam, The Netherlands
Joyce B. J. van Meurs
Affiliation:
Department of Internal Medicine, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CARotterdam, The Netherlands
Bastiaan T. Heijmans
Affiliation:
Department of Molecular Epidemiology, Leiden University Medical Centre, Postbus 9600, 2300 RCLeiden, The Netherlands
Régine P. M. Steegers-Theunissen*
Affiliation:
Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CARotterdam, The Netherlands Department of Paediatrics, Division of Neonatology, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CARotterdam, The Netherlands
*
Address for correspondence: Régine P. M. Steegers-Theunissen, MD, PhD, Professor in Periconception Epidemiology, Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CA, Rotterdam, The Netherlands. Email: r.steegers@erasmusmc.nl
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Abstract

Epigenetic programming is essential for lineage differentiation, embryogenesis and placentation in early pregnancy. In epigenetic association studies, DNA methylation is often examined in DNA derived from white blood cells, although its validity to other tissues of interest remains questionable. Therefore, we investigated the tissue specificity of epigenome-wide DNA methylation in newborn and placental tissues. Umbilical cord white blood cells (UC-WBC, n = 25), umbilical cord blood mononuclear cells (UC-MNC, n = 10), human umbilical vein endothelial cells (HUVEC, n = 25) and placental tissue (n = 25) were obtained from 36 uncomplicated pregnancies. Genome-wide DNA methylation was measured by the Illumina HumanMethylation450K BeadChip. Using UC-WBC as a reference tissue, we identified 3595 HUVEC tissue-specific differentially methylated regions (tDMRs) and 11,938 placental tDMRs. Functional enrichment analysis showed that HUVEC and placental tDMRs were involved in embryogenesis, vascular development and regulation of gene expression. No tDMRs were identified in UC-MNC. In conclusion, the extensive amount of genome-wide HUVEC and placental tDMRs underlines the relevance of tissue-specific approaches in future epigenetic association studies, or the use of validated representative tissues for a certain disease of interest, if available. To this purpose, we herewith provide a relevant dataset of paired, tissue-specific, genome-wide methylation measurements in newborn tissues.

Keywords

EWAStissue specificityHUVECumbilical cord bloodplacenta
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 12 , Issue 1 , February 2021 , pp. 113 - 123
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Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2020

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