Warwick, Alasdair Neil;
(2023)
Epidemiology and Genetics of Age-Related Macular Degeneration.
Doctoral thesis (Ph.D), UCL (University College London).
Preview |
Text
warwick_Thesis.pdf - Other Download (26MB) | Preview |
Abstract
Background: Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. Advanced AMD has two main forms - neovascular AMD (nAMD) and geographic atrophy. While an effective treatment for nAMD is now available, there is still no cure for either form. There is therefore an urgent need to optimise visual outcomes and develop new treatments. Objectives: To (i) assess real world visual outcomes for treated nAMD patients (ii) further our understanding of both genetic and non-genetic risk factors for AMD, and (iii) evaluate different Mendelian randomisation (MR) approaches to drug target prioritisation. Methods and Outputs: To address objective (i) I analysed a multicentre ophthalmic electronic health records (EHR) dataset to show how visual outcomes have improved over the past decade for UK patients with nAMD, mainly because of earlier intervention. I furthermore developed a simulation model to estimate the national impact of delayed treatment during the global pandemic. For objective (ii) I characterised individuals in the UK Biobank (UKBB) cohort who were found to have AMD-associated features on retinal imaging. I then performed a genome-wide association study (GWAS) and a phenome-wide association study (PheWAS). The underlying R code for all UKBB analyses was developed as software packages to support future work. Finally, I approached objective (iii) by utilising publicly available GWAS summary statistics to undertake a MR PheWAS, assessing the causal relevance of C-reactive protein to a range of phenotypic traits, including AMD. Conclusions: I have demonstrated how large EHR, imaging and genetic datasets can be leveraged to provide important public health messages and novel insights to disease pathogenesis. I have also presented a new MR method for drug target prioritisation. This work adds to what is already known for AMD and much of the output has broader applications.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Epidemiology and Genetics of Age-Related Macular Degeneration |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10163613 |
Archive Staff Only
 |
View Item |
