The Genetics of Ocular Endophenotypes of Primary Open Angle Glaucoma in Latinos

Intraocular pressure (IOP) and vertical cup-disc ratio (VCDR) are two quantitative traits routinely examined during ocular examinations to monitor and diagnose glaucoma, a leading cause of irreversible blindness worldwide. Findings from previous studies have demonstrated genetic factors influence these traits but such studies were conducted in European and Asian populations. The purpose of this dissertation is to address the current gaps in research regarding the genetic factors and biological mechanisms underlying the pathogenesis of glaucoma and related quantitative traits in Latinos. In the first study, we identified a significant association between African ancestry and IOP with increasing proportions of African ancestry associated with increasing IOP in Latinos. This association was modified by a significant interaction between African ancestry and hypertension. For the second study, we identified two genome-wide significant genetic markers associated with VCDR and replicated previously identified genomic regions associated with VCDR. In the third study, we identified several suggestive interactive associations between genetic markers and body mass index on VCDR that are biologically plausible candidate genomic regions for further examination. And for the fourth study, we observed significant associations between VCDR genetic risk scores and VCDR, with a higher genetic risk score associated with larger VCDR. Moreover, the VCDR genetic risk scores were associated with glaucoma and increased the discriminatory ability for glaucoma. These studies represent the first reports to investigate the association between genetic factors and ocular traits in a Latino population. Findings from this dissertation not only furthers our understanding of the genetic architecture of quantitative traits of glaucoma but also sheds new light on the biological mechanisms of glaucoma and may translate into public health prevention strategies.