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Life sciences · Journal article
World Journal of Pediatrics · September 15, 2026
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Abstract 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.