Childhood DNA methylation as a marker of early life rapid weight gain and subsequent overweight

High early postnatal weight gain has been associated with childhood adiposity, however the mechanism remains unknown. DNA methylation is a hypothesised mechanism linking early life exposures and subsequent disease. However, epigenetic changes associated with high early weight gain have not previously been investigated. Our aim was to investigate the associations between early weight gain, peripheral blood DNA methylation, and subsequent overweight/obese. Data from the UK Avon Longitudinal study of Parents and Children (ALSPAC) cohort were used to estimate associations between early postnatal weight gain and epigenome-wide DNA CpG site methylation (Illumina 450K Methylation Beadchip) in blood in childhood (n= 125) and late adolescence (n= 96). High weight gain in the first year (a change in weight z‐scores >0.67), both unconditional (rapid weight gain) and conditional on birthweight (rapid thrive), were related to individual CpG site methylation and across regions using the meffil pipeline, with and without adjustment for cell type proportions, and with 5% false discovery rate correction. Variation in methylation at high weight gain associated CpG sites were then examined with regards to body composition measures in childhood and adolescence. Replication of the differentially methylated CpG sites was sought using whole-blood DNA samples from 104 children from the UK Southampton Women’s Survey.