This review article on the genetics of primary open-angle glaucoma (POAG) notes that genetic studies are one approach to identify the molecules and pathways involved in glaucoma disease pathogenesis.
The authors report that while glaucoma currently is clinically defined, its exact etiology is unknown. Most cases of POAG are believed to be caused by multiple genetic and environmental factors.
They explain that familial aggregation of POAG has long been recognized, and the analysis of POAG families with a Mendelian inheritance form of this disease has been used to identify multiple loci linked to these families. Some causative genes, such as myocilin, optineurin and WD repeat domain 36, have been identified.
Several genetic linkage or association studies have been conducted for candidate genes and genetic regions, finding some that have strong relations to specific phenotypes, such as early onset or elevated IOP. Others are associated with POAG irrespective of IOP and phenotypic variation.
Although recent genome-wide association studies have identified new susceptibility loci for POAG, the authors note that genetic regions identified by linkage analysis are sometimes too large to enable a clear identification of the real causative genes, and susceptibility variants identified by association studies may only be markers on the genetic region. After identification of a genetic region, confirmation of reproducibility, identification of truly causative variants or genes, and evidence for functional involvement are needed.
While further investigation is required to clarify the precise contribution of specific genes identified to the pathogenesis of glaucoma, the evidence provided by genetic studies is expected to improve current understanding of the etiology of glaucoma and facilitate the development of diagnostic and therapeutic strategies.