2066-P: Exploring the Association between Cord Blood DNA Methylation and Childhood Adiposity: Insights from an Epigenome-Wide Association Study in the HAPO Follow-Up Study

Introduction and Objective: Intrauterine exposure to gestational hyperglycemia is associated with greater offspring adiposity, but the mechanisms are unclear. A potential mechanism is early life DNA methylation (DNAm). We hypothesized that differential cord blood (CB) DNAm is associated with peripubertal adiposity. Methods: Using a multinational longitudinal birth cohort, we conducted a discovery epigenome wide association study (EWAS) using the Illumina 850K beadchip. CB DNAm (as M-values) were the predictor; outcomes included childhood serum leptin (n=882) and direct adiposity measures at 10-14 years of age (mean 11.5): BMI z-score, sum of skinfolds (SSF), waist circumference (WC), and air displacement plethysmography bodyfat%, n=2597-2937. Benjamini-Hochberg FDR-adjusted p0.05 defined statistical significance. Regression models adjusted for maternal and child covariates including maternal glucose and BMI, cell types, and ancestry. Results: Eleven CpG sites were significantly associated with WC and one with serum leptin (Table 1). A CpG site near AHAK2, a gene involved in body fat regulation, was associated with WC. There were no associations between CB DNAm and BMI z-score, SSF, or bodyfat%. Conclusion: CB DNAm marks on several genes, including AHNAK2, are associated with WC and serum leptin levels 10-14 years later. Disclosure S. DeLacey: None. Y. Liu: None. W. Lowe: None. M. Hivert: None. D. Scholtens: None. J. Josefson: None. Funding Ruth L. Kirschstein National Research Service Award T32 (DK007169), National Institutes of Health (R01DK118403), National Institutes of Health (UL2TR001422).