Neonatal Bloodspot DNA Methylation Patterns are Associated with Childhood Weight Status in the Healthy Families Project

BACKGROUND: This study measured longitudinal DNA methylation dynamics at growth-related genes during childhood, and then tested whether DNA methylation at various stages of childhood was associated with obesity status. METHODS: Using neonatal bloodspot (n=132) and matched childhood blood samples (n=65), DNA methylation was quantified at a repetitive element (LINE-1), two imprinted genes (IGF2, H19), and four non-imprinted genes (LEP, PPARA, ESR1, SREBF1) related to growth and adiposity. Logistic regression was used to test whether neonatal bloodspot DNA methylation at target genes was associated with log odds of obesity (Y/N) in children recruited from three age groups – 12–24 months old (n=40), 3–5 years of age (n=40), and 10–12 years of age (n=52). RESULTS: In 3–5 year olds, neonatal bloodspot LINE-1 methylation was negatively associated with obesity (log odds = −0.40, p=0.04). Across childhood age group in matched blood samples, DNA methylation levels in blood decreased (p<0.05) at LINE-1, PPARA, ESR1, SREBF1, IGF2, and H19, and increased (p<0.05) at LEP. CONCLUSIONS: Our results suggest that age-related epigenetic changes occur at growth-related genes in the first decade of life, and that gene-specific neonatal bloodspot DNA methylation may be a useful biomarker of obesity likelihood during childhood.