Bioinformatic analysis of obesity related epigenetic targets

Abstract

Epigenetic modifications are involved in the maintenance of tissues, achieved without the need to alter the underlying genomic sequence. In this thesis, I focus on DNA methylation and the changes which occur in obese and post-obese individuals. The main aim of my analysis was to identify methylation changes which were correlated with alterations in BMI values. To accomplish this, three principal analyses were undertaken. A reanalysis was performed on three published data sets, enabling the detection of unique obesity-related targets susceptible to methylation change due to fluctuations in adiposity.

In the first comparative analysis (Arner et al., 2015), an investigation of the methylation profile difference between control (non-obese) and obese females, at both a global and region-specific level was carried out. Hypermethylation in this analysis was found to be synonymous with the obese state. Strong associations were observed between hypermethylated genes in obesity and metabolic diseases. This link was further strengthened by two significant genes targets which were tightly aligned to the metabolic disease class.

A comparative analysis (Arner et al., 2015; Dahlman et al., 2015) was performed to identify obesityrelated gene targets which were highly sensitive to changes in BMI. These included overlapping gene body targets demonstrating increased methylation in obesity and decreased methylation at the same CpG loci following surgery induced weight-loss. Metabolic disease was strongly associated with this analysis. Additionally, two gene targets identified between obese and post-obese data, were significantly associated with the cardiovascular disease class. Demonstrating a clear connection between the methylation profile of identified obesity-related gene targets and diseases commonly attributed to obesity.

The final analysis (Fraszczyk et al., 2020), focused on the comparison of white adipose tissue and whole blood. Both tissue types are commonly used in methylation data profiling for obesity-related studies. Through this comparison, common obesity-related targets were identified, which exhibited the same
methylation directional change post-bariatric surgery in both tissue type data. As methylation targets were detected in both tissue types, this may enhance our understanding of the role methylation plays in the development and/or regulation of obesity comorbidities.

Date of Award	Sept 2021
Original language	English
Supervisor	Colum Walsh (Supervisor), Gerard Mc Mahon (Supervisor) & Gareth Davison (Supervisor)