Study title

We obtained newly-generated genome-wide DNA methylation profiles from whole blood in 240 individuals from the TwinsUK cohort. DNA methylation levels were profiled at 38-86 years of age using the Infinium MethylationEPIC BeadChip. Epigenetic mechanisms such as DNA methylation are key regulators of gene function. Epigenetic signals are malleable and can change in response to internal and external stimuli. The epigenome thereby provides a mechanism of interaction between the genome with the environment, and we hypothesize that early life stimuli and exposures over the life course leave an epigenetic mark. The proposal will explore DNA methylation in 4,024 samples from four British cohort studies (the MRC National Survey for Health and Development (NSHD) or 1946 birth cohort, the National Child Development Study (NCDS) or 1958 birth cohort, the 1970 British Cohort Study (BCS70), and the TwinsUK cohort (TwinsUK)) in order to identify epigenetic signatures of early life experience and exposure to social, environmental, and biological stimuli over the life course, linking findings to changes in physical and cognitive function during ageing. Each study captures a range of early life experiences, longitudinal health measures and lifestyle questionnaire data from adult life, DNA samples collected at single or multiple time-points, and in a sample subset, multiple genomic data for follow-up analyses. The primary research design is a prospective analysis of longitudinal data across 2,336 blood and 1,688 buccal samples from the four cohorts. The first aim of the research will be to establish whether biological, environmental, and social stimuli in early life and over the life course result in detectable differences in DNA methylation profiles in adults. We will consider whether there are epigenetic associations with a number of factors including biological, environmental and social factors in utero and in early childhood (e.g. birthweight, childhood growth, maternal smoking...