1215-P: Maternal Glycemia Associations with Cord Blood DNA Methylation in the Hyperglycemia and Adverse Pregnancy Outcome Study

Maternal hyperglycemia during pregnancy is associated with impaired offspring glycemia later in life. Differential methylation of offspring DNA could be an underlying mechanism for this association. Using data from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study, a large, international, mother-child cohort, we conducted an epigenome-wide association study to identify associations between maternal glucose sum of z-scores from a fasting 2-hr oral glucose tolerance test (OGTT) during pregnancy (mean 27.6 wks gestation) and offspring cord blood DNA methylation (cb DNAm). We analyzed cb DNAm with Illumina EPIC arrays (791,359 CpG sites after QC) on 3,041 HAPO samples. Using linear regression models adjusted for maternal covariates and field center, we identified 16 CpG sites after accounting for multiple testing (Bonferroni-adjusted p0.05). The significant associations included two CpG sites near TXNIP, a gene that encodes the thioredoxin-interacting protein, which is involved in glucose-sensing. Our analyses identified new loci in addition to external validation of previous findings identifying TXNIP as a differentially methylated locus in relation to in utero exposure to hyperglycemia. These findings support DNA methylation as a potential mechanism underlying the association between maternal hyperglycemia and programming of offspring metabolic health. Disclosure M.E. Bianco: None. W.L. Lowe: None. J.L. Josefson: None. D. Scholtens: None. M. Hivert: None. M. Gurra: None. Funding National Institutes of Health (R01DK118403)