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dc.titleChoice of surrogate tissue influences neonatal EWAS findings
dc.contributor.authorLin X.
dc.contributor.authorTeh A.L.
dc.contributor.authorChen L.
dc.contributor.authorLim I.Y.
dc.contributor.authorTan P.F.
dc.contributor.authorMacIsaac J.L.
dc.contributor.authorMorin A.M.
dc.contributor.authorYap F.
dc.contributor.authorTan K.H.
dc.contributor.authorSaw S.M.
dc.contributor.authorLee Y.S.
dc.contributor.authorHolbrook J.D.
dc.contributor.authorGodfrey K.M.
dc.contributor.authorMeaney M.J.
dc.contributor.authorKobor M.S.
dc.contributor.authorChong Y.S.
dc.contributor.authorGluckman P.D.
dc.contributor.authorKarnani N.
dc.identifier.citationLin X., Teh A.L., Chen L., Lim I.Y., Tan P.F., MacIsaac J.L., Morin A.M., Yap F., Tan K.H., Saw S.M., Lee Y.S., Holbrook J.D., Godfrey K.M., Meaney M.J., Kobor M.S., Chong Y.S., Gluckman P.D., Karnani N. (2017). Choice of surrogate tissue influences neonatal EWAS findings. BMC Medicine 15 (1) : 211. ScholarBank@NUS Repository.
dc.description.abstractBackground: Epigenomes are tissue specific and thus the choice of surrogate tissue can play a critical role in interpreting neonatal epigenome-wide association studies (EWAS) and in their extrapolation to target tissue. To develop a better understanding of the link between tissue specificity and neonatal EWAS, and the contributions of genotype and prenatal factors, we compared genome-wide DNA methylation of cord tissue and cord blood, two of the most accessible surrogate tissues at birth. Methods: In 295 neonates, DNA methylation was profiled using Infinium HumanMethylation450 beadchip arrays. Sites of inter-individual variability in DNA methylation were mapped and compared across the two surrogate tissues at birth, i.e., cord tissue and cord blood. To ascertain the similarity to target tissues, DNA methylation profiles of surrogate tissues were compared to 25 primary tissues/cell types mapped under the Epigenome Roadmap project. Tissue-specific influences of genotype on the variable CpGs were also analyzed. Finally, to interrogate the impact of the in utero environment, EWAS on 45 prenatal factors were performed and compared across the surrogate tissues. Results: Neonatal EWAS results were tissue specific. In comparison to cord blood, cord tissue showed higher inter-individual variability in the epigenome, with a lower proportion of CpGs influenced by genotype. Both neonatal tissues were good surrogates for target tissues of mesodermal origin. They also showed distinct phenotypic associations, with effect sizes of the overlapping CpGs being in the same order of magnitude. Conclusions: The inter-relationship between genetics, prenatal factors and epigenetics is tissue specific, and requires careful consideration in designing and interpreting future neonatal EWAS. Trial registration: This birth cohort is a prospective observational study, designed to study the developmental origins of health and disease, and was retrospectively registered on 1 July 2010 under the identifier NCT01174875. © 2017 The Author(s).
dc.publisherBioMed Central Ltd.
dc.subjectDNA methylation
dc.subjectEpigenome-wide association study
dc.subjectPrenatal factors
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.contributor.departmentDEPT OF PHYSIOLOGY
dc.contributor.departmentDEPT OF PAEDIATRICS
dc.contributor.departmentDEPT OF OBSTETRICS & GYNAECOLOGY
dc.contributor.departmentDEPT OF MEDICINE
dc.contributor.departmentSAW SWEE HOCK SCHOOL OF PUBLIC HEALTH
dc.contributor.departmentDEPT OF BIOCHEMISTRY
dc.description.sourcetitleBMC Medicine
dc.grant.fundingagencyNational Medical Research Council
dc.description.seriesGUSTO (Growing up towards Healthy Outcomes)
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