Epigenetic changes are associated with the development of non-communicable diseases, including obesity related disease and type 2 diabetes. Experimental studies have suggested that the early life environment makes a significant contribution to an individual’s risk of developing obesity, through the altered epigenetic regulation of genes.
In human populations, progressive identification of DNA methylation loci associated with obesity and related phenotypes is occurring. However, despite this, the role of the methylome in mediating early life environmental exposures on obesity and related diseases remains challenging. Gaps in knowledge include uncertainty as to variability of the methylome after birth, the relative contribution of genetic and epigenetic influences on fetal programming and contribution of cell heterogeneity.
In this talk, we discuss within the context of longitudinal birth cohorts (Raine Study, Southampton Women’s Survey, Singapore GUSTO cohort, Epigenetics Consortia), studies identifying DNA methylation loci associated with obesity and diabetes-related phenotypes.
The Western Australia Pregnancy Cohort (RAINE) study (www.rainestudy.org.au) recruited 2900 pregnant women between 1989 and 1992. The offspring born to these women have longitudinal exposure data, and adiposity phenotypes. Follow-up of the offspring has been undertaken at birth, 1, 2, 3, 5, 8, 10, 14, 17 and 24 years. Fasting samples, including insulin and glucose were measured at 8, 14, 17 and 24 years. During adolescence, all subjects have datasets derived from Illumina Infinium HumanMethylation450 BeadChips and mass spectrometry based metabolomics. Early life environmental exposures (maternal BMI, gestational weight gain, maternal smoking in pregnancy, maternal stress, breast feeding) have been prospectively recorded in this cohort,
The roles of early environmental exposures in mediating the association between the methylome and adiposity are being investigated. Current focus is on dissecting out the complex interplay between fixed genetic influences, epigenetics and the early life environment on subsequent obesity and type 2 diabetes risk, using higher order –omics data.