Abstract
Glioma is the most common type of brain tumour (BT) and results in significant years of life lost. The risk profile of glioma is largely unknown, and there has been little innovation in treatments and therapies available for glioma. These points were expanded upon in Chapter 1.This thesis conceptualised a pipeline which combined population-level and multi-omic data with causal inference analyses and traditional and pharmaco-epidemiological techniques. Methods and relevant datasets were described in Chapters 2 & 3.
Analyses in Chapter 4 utilised a combined Mendelian randomisation (MR) and colocalisation framework to provide causal evidence for germline genetic variants associated with gene expression levels that affect glioma risk.
Chapter 5 leveraged the same framework with germline genetic variants associated with protein abundance levels. Results were combined with results from the previous Chapter and, with supporting evidence from the literature, inform on putative chemopreventive targets for glioma.
The pharmaco-epidemiological analyses in Chapter 6 provided evidence that exposure to glitazones, a family of anti-type 2 diabetic medications, reduced risk of primary and secondary BT, highlighting these drugs as potential agents for re-purposing.
Chapter 7 concluded that, altogether, analyses presented in this thesis may be combined to form a drug target identification, prioritisation and re-repurposing pipeline to improve patient outcomes in the clinic.
| Date of Award | 28 Sept 2021 |
|---|---|
| Original language | English |
| Awarding Institution |
|
| Supervisor | Kathreena M Kurian (Supervisor), Richard M Martin (Supervisor), Caroline Relton (Supervisor), Jie Zheng (Supervisor) & Kaitlin H Wade (Supervisor) |