Asparaginase methylation and childhood obesity: cross-tissue patterns and parent–child concordance in a prospective cohort

BACKGROUND: Early-life epigenetic mechanisms may contribute to the developmental programming of childhood obesity. We aimed to examine whether placental asparaginase (ASPG) DNA methylation (DNAm) is associated with adiposity at 6 years of age and to explore its cross-tissue patterns and parent-child concordance. METHODS: In a prospective birth cohort, placental ASPG DNAm was quantified by pyrosequencing and related to anthropometric and cardiometabolic outcomes in children at 6 years (n = 180). DNAm was also measured in child peripheral blood (n = 127) and in maternal and paternal blood samples during pregnancy (n = 44). RESULTS: Increased placental ASPG DNAm was associated with increased adiposity and cardiometabolic markers at 6 years and increased odds of overweight/obesity [odds ratio (OR) = 1.06, 95% confidence interval (CI) = 1.01-1.11, P = 0.01]. Similar associations were observed for child blood (OR = 1.19, 95% CI = 1.04-1.36, P = 0.01), although these analyses were cross-sectional. Placental and child DNAm levels were positively correlated (r = 0.40, P < 0.01), and maternal-child DNAm was concordant (r = 0.48, P < 0.01), although the parental analyses were exploratory and based on a limited sample size (n = 44). CONCLUSIONS: ASPG DNAm is associated with childhood adiposity and shows cross-tissue and parent-child concordance, suggesting its potential role as an early-life epigenetic marker associated with metabolic risk. Given the modest effect sizes and exploratory nature of some analyses, these findings warrant cautious interpretation and require replication in independent cohorts.