Investigating the genetic complexity of glaucoma

Glaucoma is an age-related chronic eye disease that damages the optic nerve, a cranial nerve that is pivotal for vision. Primary open-angle glaucoma (POAG) represents the most prevalent type of this disease and its prevalence varies between populations. It ranges from 1 to 4% in Europe and from 2 to 7% in African countries in adults aged 40 years and over. The condition is asymptomatic in its early stages, a peculiarity that explains why most of the cases are initially unaware of having this disease and are left undiagnosed. Many risk factors for POAG have been recognised. The most widely acknowledged include: advanced age, elevated intraocular pressure, having African descent, positive family history of glaucoma, and thin central corneal thickness. Genetic studies conducted in twins, families, and populations revealed that POAG is a heterogeneous complex disease with a large heritable component. So far, despite the vast and constantly increasing genetic investigation, the identified loci explain only 10% of POAG risk, predominately in European and Asian populations. For this reason, in individuals of African ancestry most of the variants already identified do not seem to play a role in the disease, which suggests a population-specific genetic architecture. Clearly, there is still a large portion of missing and hidden heritability to be found. The aim of the research presented here was to investigate different genetic risk factors contributing to glaucoma susceptibility that may explain part of the missing heritability. The sources of these risk factors included the analysis of ethnic risk, common variants, mutations, variations in copy number in the nuclear and analysis of mitochondrial genome