Abstract
This thesis, presented as a thesis incorporating publications, examines the genetic epidemiology of pigmentary glaucoma and related ocular phenotypes. The focus is on sporadic pigmentary glaucoma, the most prevalent form of secondary open-angle glaucoma, utilising data from multiple cohorts across the globe. Although it is not common, pigmentary glaucoma has a relatively young age of onset, resulting in a disproportionately high disease burden as patients are at risk of a greater number of years of irreversible loss of vision. A greater understanding of the genetic epidemiology can lead to a better understanding of pathophysiology, and in turn could lead to improvements in treatment and the identification of those at risk.The current literature on pigmentary glaucoma genetics has been centred on familial studies with highly penetrant genetic risk factors, rare at the population level, following a Mendelian pattern of inheritance. In this thesis, I first identify that common genetic variation accounts for 45% of disease risk in unrelated cases, and subsequently identify the first two genetic loci associated with disease among the general population.
In other analyses, I investigate the genetic architecture of ocular features including pigmentation, myopia, and corneal morphology which are known associated risk factors for pigmentary glaucoma and may affect disease onset and progression. I identify hundreds of novel associations and establish a better understanding of their genetic aetiology. This in turn provides greater clarity on the shared genetic architecture between these traits with pigmentary glaucoma, and how they may influence disease. Most importantly, this work led to the demonstration that myopia exerts direct causal effects in the development of pigment dispersion syndrome and pigmentary glaucoma.
| Date of Award | 1 Dec 2021 |
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| Original language | English |
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| Supervisor | Chris Hammond (Supervisor) & Pirro Hysi (Supervisor) |