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.