Associations between imprinted gene differentially methylated regions, appetitive traits and body mass index in children

摘要

Background: Knowledge regarding genetic influences on eating behaviours is expanding; yet less is known regarding contributions of epigenetic variation to appetitive traits and body mass index (BMI) in children. Objective: The purpose of this study was to explore relationships between methylation at differentially methylated regions (DMRs) of imprinted genes [insulin-like growth factor 2/H19 and Delta-like, Drosophila, homolog 1'/maternally expressed gene 3) using DNA extracted from umbilical cord blood leucocytes, two genetically influenced appetitive traits (food responsiveness and satiety responsiveness) and BMI. Methods: Data were obtained from participants (N = 317; mean age = 3.6 years; SD = 1.8 years) from the Newborn Epigenetic STudy. Conditional process models were implemented to investigate the associations between DMRs of imprinted genes and BMI, and test whether this association was mediated by appetitive traits and birthweight and moderated by sex. Results: Appetitive traits and birthweight did not mediate the relationship between methylation at DMRs. Increased insulin-like growth factor 2 DMR methylation was associated with higher satiety responsiveness. Higher satiety responsiveness was associated with lower BMI. Associations between methylation at DMRs, appetitive traits and BMI differed by sex. Conclusions: This is one of the first studies to demonstrate associations between epigenetic variation established prior to birth with appetitive traits and BMI in children, providing support for the need to uncover genetic and epigenetic mechanisms for appetitive traits predisposing some individuals to obesity.