What question did this study set out to answer?

The aim is to investigate the relationship between cord blood DNA methylation and childhood adiposity.

June 13, 2026

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

Key Points

The aim is to investigate the relationship between cord blood DNA methylation and childhood adiposity.
Conducted a multinational longitudinal epigenome-wide association study using the Illumina 850K beadchip.
Assessed outcomes including serum leptin and adiposity measures at ages 10-14 in a sample size ranging from 882 to 2937.
Employed regression models to adjust for maternal and child covariates.
Identified eleven CpG sites significantly associated with waist circumference.
One CpG site near the AHNAK2 gene, linked to body fat regulation, was associated with waist circumference.
No significant associations found between cord blood DNA methylation and BMI z-score, skinfolds, or body fat percentage.

Abstract

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).

Mark Helpful

Bookmark

Relay