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Title: Early life risk factors and epigenetic biomarkers of obesity across the life course
Authors: Robinson, Natassia
Issue Date: 2020
Publisher: Newcastle University
Abstract: Obesity prevalence continues to rise and can be partially attributed to the obesogenic environment. However, there is increasing evidence that environmental exposures in early development can influence later-life disease, known as the Developmental Origins of Health and Disease hypothesis. Whilst some early life exposures have been associated with later-life adiposity, the underlying mechanism is less understood. One hypothesised mechanism is through epigenetic changes, such as DNA methylation. Multiple longitudinal cohorts were used to investigate the hypothesis; DNA methylation is a mediating mechanism between early life events and subsequent obesity. The Newcastle Thousand Families (NTFS) and Gateshead Millennium (GMS) studies (established 1947 and 2000 respectively), were used to investigate the impact of early life exposures (i.e. socioeconomic status, growth, adversity) on childhood (GMS) and adult (NTFS) obesity. Using both cohorts provided an opportunity to investigate regional temporal changes on childhood obesity, and the impact of obesogenic environments. The Avon Longitudinal study of Parents and Children (ALSPAC), which has methylation data (Illumina 450K array), was used to investigate associations between early life exposures and DNA methylation (in childhood and late adolescence) at CpG loci. Early life rapid weight gain (RWG) was consistently associated with childhood body composition in both local cohorts over time. In ALSPAC, RWG was significantly associated with a 1% increase in childhood methylation (age 7, n=116) at an individual CpG locus (CG11531579). Furthermore, the highest levels of methylation (+2%) were in those with RWG who were subsequently overweight/obese (OWOB, age 17). The CG11531579 loci was investigated further in NTFS adults (age 50, n=134) to examine whether the epigenetic marks persist. RWG was also associated with methylation changes in adults, although this was a decrease in methylation (-2%, age 50). These findings suggest that RWG in infancy is associated with small, dynamic variations in methylation at this locus.
Description: Ph. D. Thesis.
Appears in Collections:Institute of Health and Society

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