The IGM’s precision medicine initiative in eye diseases is allowing precise genetic diagnosis of childhood retinal diseases (Stargardt disease, retinitis pigmentosa, etc.) where already >200 genes have been determined as causal, and new genes are being discovered at a rapid pace. It is also deciphering the genetic components of very prevalent, late-onset retinal disorders such as age-related macular degeneration (AMD) to provide patients with genetic risk assessment and disease prognosis. In both cases, the data are used for the targeted selection of patients for clinical trials.
Ongoing studies at the CUMC Eye Institute, based on comprehensive clinical imaging and advanced NGS-based genetic analysis, allow identification of causal genes in up to 80% of early onset retinal degenerations.
Comprehensive genomic analysis has also allowed us to identify close to 40 genes/loci where both common and rare variants are associated with AMD. This highly prevalent, heritable disease affects 25% of individuals over the age of 75 and is correlated with other complex traits such as cardiovascular disease. Whole exome sequencing of large cohorts of AMD patients and matched controls under the initiative allow us to refine the genetic causality not only for the disease in general, but also for individual patients. This information will increase our understanding of rare and common genetic variation for macular degeneration biology, thereby guiding the development of therapeutic interventions, facilitating early diagnosis, monitoring and prevention of disease.