Host genetics and epigenomics of inflammatory bowel disease
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Date
2019-09-30
Authors
Power, E. M.
Journal Title
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Publisher
University College Cork
Published Version
Abstract
The overall aim of this thesis was to investigate the interaction between host-genetics and epigenetic profiles in IBD, particularly in CD. This included identifying epigenetic markers in CD patients with frequent relapses and stratifying patients by epigenetic profiles and correlating with gut microbiota profiles. This thesis also investigated genetic variation and its association with IBD, UC and CD. MeQTLs was also investigated to examine the impact of genetic variation on epigenetics. The first study objective included case/control for diseased samples and a second objective was to investigate the active cycle for Crohn’s Disease by comparing paired inflamed and non-inflamed samples.
The genetic association analysis found 11 novel SNPs associated with IBD, CD or UC located on Chromosome 6 but did not find any previous IBD susceptibility loci to be significant.
The epigenetic analysis based on differential DNA methylation found no significant signals in the case/control analysis. An inflammation factor was found to be present for studies including samples from active areas showing inflammation. MeQTLs analysis showed significant associated loci on genes SMURF1 and GNA12, both genetic susceptibility loci for IBD, CD and UC, and found to be tissue specific for the human gut.
Both the epigenetic and meQTL analysis were unable to replicate previous findings from Cooke et al (1) for the inflammation epigenetic analysis and Ventham et al (2) for the epigenetic Case/Control analysis and meQTL study.
The analysis examining association between microbiota in the gut and epigenetic changes found three genes SNX18, VWASA and RNF23 to be significantly differentially methylated according to microbiota cluster membership.
The cohort for this thesis consisted of 140 cases: 32 controls for genetic analysis and 42 cases:23 controls for epigenetic data. The low power for the genetic analysis (5% power) and epigenetic analysis (4% differential change in methylation at 80% power) suggest that increased sample size is required to increase statistical power. Additional constraints are availability of true healthy samples to act as control samples and biopsy tissue used for biological samples.
Description
Controlled Access
Keywords
Epigenetics , Genetics , Crohn's disease , Inflammatory bowel disease
Citation
Power, E. M. 2019. Host genetics and epigenomics of inflammatory bowel disease. PhD Thesis, University College Cork.