(P27-096-25) DNA Methylation of B4GALNT4 Associates With Maternal Serum Folate and Choline Concentrations and With Offspring Adiposity: The Healthy Start Study

Objectives: To investigate the relationships of maternal serum folate and choline concentrations at ~ 17 weeks' gestation, cord blood DNA methylation (DNAm) of genes in metabolic and nutrient sensing pathways, and their interaction with offspring adiposity in early life.

Methods: A sub-sample of 277 maternal-infant dyads from the Healthy Start Study were followed from early pregnancy to early childhood.  Serum concentrations of folate and choline were assessed at ~ 17 weeks’ gestation using ELISA and colorimetric assays. Using generalized linear regression, we assessed 1) the main effect of folate, 2) the main effect of choline and 3) their interaction on epigenome wide cord blood DNAm using the Illumina Infinium 450K array, followed by identification of differentially methylated regions (DMRs) using Comb-p. Cord blood DNAm of the identified hits was then assessed in association with offspring adiposity from air displacement plethysmography at birth, 5 months and 5 years of age well as the change in adiposity during these time periods.  Covariates included maternal age, pre-pregnancy BMI, prenatal smoking, mode of delivery, infant sex, and cord blood cell type composition. False discovery rate (FDR) was controlled at 0.1 using Benjamini-Hochberg.

Results: Thirty-four and 66 distinct DMRs associated with folate or choline concentrations, respectively.  Six different DMRs were associated with the joint effect of folate and choline.  These included FGFR4, B4GALNT4, EGFL8, mitochondrial HMGCL, SDK1, and PSMB9.  Of those, B4GALNT4 associated with adiposity at 5 years of age (p=0.04, q=0.06) and change in adiposity from 5 months to 5 years of age (p=0.007, q=0.07) after controlling for FDR at 0.1.

Conclusions: Maternal serum folate and choline concentrations at ~17 weeks’ gestation are associated with DMRs annotated to genes involved in cell growth, nutrient metabolism, hypothalamic peptide biosynthesis, embryonic and anatomical development and mitochondrial function.  It is the joint effect of these two nutrients, however, that is associated with cord blood DNAm of B4GALNT4, a genomic region previously and presently shown to associate with adiposity in early infancy and childhood in Healthy Start.  Our work suggests a potential mediating pathway of folate to DNAm of B4GALNT4 to offspring adiposity in early life, but only in the presence of choline. 

Funding Sources: NIDDK