The Effects of Childhood Malnutrition on DNA Methylation in Adulthood

Abstract

Insults during critical periods of development could result in epigenetic changes affecting health and behavioral outcomes throughout the lifespan. To address the epigenetic effects of childhood malnutrition we assessed genome-wide DNA methylation levels in previously malnourished and healthy control adults (age 33-47 yrs). The Barbados Nutrition Study is a 47-year longitudinal study, following individuals with histories of malnutrition limited to the first year of life - who were enrolled in an intervention program through 12 years of age – and healthy controls from the same classrooms and neighborhoods. Using the Illumina 450K array and a stringent statistical analysis with age, gender and cell composition correction, we report differences in DNA methylation between previously malnourished (n=52) and controls (n=44). Differentially Methylated Regions (DMRs) were identified using a 1 kb sliding window approach, with significant DMRs comprising multiple CpGs selected at FDR<0.05. In total we identified 303 DMRs, including several genes with known roles in regulating metabolism. Loci with the largest differences between Malnourished and Control (as measured by methylation values) included GNAS, an imprinted gene regulating metabolism and obesity. Our data show that epigenomic changes in genes affecting nutrient metabolism are detected in white blood cells of adults exposed to a single episode of malnutrition in early childhood. Acknowledgements: This research was supported by NIH grant HD060986 (JRG) and R01MH086509 (SA).