Epigenetic markings play a major role in the expression of genetic traits but are not encoded in the DNA sequence of the genome, instead epigenetic information is carried in the form of chemical modifications to DNA, including methylation.

Epigenetic patterns change across the lifecourse and appear to be especially plastic in early life. Changes are also observed in later life although these appear to be limited mainly in non-coding regions of the genome harbouring repeat sequence motifs. The functional relevance of these various epigenetic alterations requires investigation. Evidence is mounting to illustrate that the epigenome 'captures' environmental exposures but little is known about how relevant this is to the pathogenesis of common complex disease or to the ageing trajectory.

Differentially methylated regions (DMRs) will be identified using MeDIP-sequencing on sets of 20 samples from multiple sample points (e.g. 0, 7y, 15y, 30y, 40y, 50y) to capture the full age distribution across the cohort and will include serial samples from the same ALSPAC mothers and children. A 384-plex panel of age-related DMRs will be taken forward for analysis on as many of the ALPSAC cohort as is plausible within the budget, currently estimated at 2,000-3,000 samples at multiple timepoints (n=7).

Data analysis will include modelling of epigenetic changes across the lifecourse as well as the development of MR-based analysis tools to incorporate DNA methylation data. The data set arising will be used to address the determinants of epigenetic patterns at specific time points, the factors driving their change over time and the subsequent consequences for health and disease in later life.