Maternal Glycemic Dysregulation During Pregnancy and Neonatal Blood DNA Methylation: Meta-analyses of Epigenome-Wide Association Studies

Maternal glycemic dysregulation during pregnancy increases the risk of adverse health outcomes in her offspring, a risk thought to be linearly related to maternal hyperglycemia. It is hypothesized that changes in offspring DNA methylation (DNAm) underline these associations. To address this hypothesis, we conducted fixed-effects meta-analyses of epigenome-wide association study (EWAS) results from eight birth cohorts investigating relationships between cord blood DNAm and fetal exposure to maternal glucose (Nmaximum= 3,503), insulin (Nmaximum= 2,062), and area under the curve of glucose (AUCgluc) following oral glucose tolerance tests (Nmaximum = 1,505). Inflation and bias was addressed with the bacon Bioconductor package for individual cohorts and the meta-analysis results and reported model estimates and standard errors are adjusted. Greater maternal AUCgluc during pregnancy was associated with lower cord blood DNAm at neighboring CpGs cg26974062 and cg02988288 in TXNIP. Follow-up analyses show that these changes may have functional and later-life consequences and warrant further mediation and causal analysis. 

The corresponding paper can be found here: https://doi.org/10.2337/dc21-1701.

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