DNA methylation changes in cord blood and the developmental origins of health and disease – a systematic review and replication study

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dc.contributor.authorAkhabir, Loubna
dc.contributor.authorStringer, Randa
dc.contributor.authorDesai, Dipika
dc.contributor.authorMandhane, Piush J.
dc.contributor.authorAzad, Meghan B.
dc.contributor.authorMoraes, Theo J.
dc.contributor.authorSubbarao, Padmaja
dc.contributor.authorTurvey, Stuart E.
dc.contributor.authorParé, Guillaume
dc.contributor.authorAnand, Sonia S.
dc.date.accessioned2022-04-01T09:11:38Z
dc.date.issued2022-03-19
dc.date.updated2022-04-01T09:11:39Z
dc.description.abstractAbstract Background Environmental exposures in utero which modify DNA methylation may have a long-lasting impact on health and disease in offspring. We aimed to identify and replicate previously published genomic loci where DNA methylation changes are attributable to in utero exposures in the NutriGen birth cohort studies Alliance. Methods We reviewed the literature to identify differentially methylated sites of newborn DNA which are associated with the following five traits of interest maternal diabetes, pre-pregnancy body mass index (BMI), diet during pregnancy, smoking, and gestational age. We then attempted to replicate these published associations in the Canadian Healthy Infant Longitudinal Development (CHILD) and the South Asian birth cohort (START) cord blood epigenome-wide data. Results We screened 68 full-text articles and identified a total of 17 cord blood epigenome-wide association studies (EWAS) of the traits of interest. Out of the 290 CpG sites reported, 19 were identified in more than one study; all of them associated with maternal smoking. In CHILD and START EWAS, thousands of sites associated with gestational age were identified and maintained significance after correction for multiple testing. In CHILD, there was differential methylation observed for 8 of the published maternal smoking sites. No other traits tested (i.e., folate levels, gestational diabetes, birthweight) replicated in the CHILD or START cohorts. Conclusions Maternal smoking during pregnancy and gestational age are strongly associated with differential methylation in offspring cord blood, as assessed in the EWAS literature and our birth cohorts. There are a limited number of reported methylation sites associated in more than two independent studies related to pregnancy. Additional large studies of diverse populations with fine phenotyping are needed to produce robust epigenome-wide data in order to further elucidate the effect of intrauterine exposures on the infants’ methylome.
dc.identifier.citationBMC Genomics. 2022 Mar 19;23(1):221
dc.identifier.urihttps://doi.org/10.1186/s12864-022-08451-6
dc.identifier.urihttp://hdl.handle.net/1993/36380
dc.language.rfc3066en
dc.rightsopen accessen_US
dc.rights.holderThe Author(s)
dc.titleDNA methylation changes in cord blood and the developmental origins of health and disease – a systematic review and replication study
dc.typeJournal Article
local.author.affiliationRady Faculty of Health Sciencesen_US
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