Principal Investigator: Professor Ayellet Segre
Massachusetts Eye and Ear Infirmary (USA)Tags: 50211, functional genomics, gene set enrichment analysis, genome-wide association studies (GWAS), Machine Learning, Ocular diseases, polygenic risk models
The overall goal of this proposal is to identify new methods to detect and treat patients with high risk of developing diseases causing blindness. Age-related blinding diseases negatively impact quality of life for many people and are a significant burden on health care delivery and medical costs throughout the world. This burden will increase significantly in the coming decades with the aging of the global populations. Especially significant is the burden of diseases causing decreased vision in countries with limited resources for disease detection and treatment. We will use genetic analyses to find genes that influence disease risk. We will investigate interactions among disease-related genes and will identify the biological pathways and regulatory mechanisms that are impacted by the disease-related genetic risk factors. The discovery of genes and pathways can point to targets for new therapies directed at the primary causes of disease. To develop better methods to detect patients at risk for disease we will explore machine learning approaches to create new screening tests that combine genetic risk factors with ocular image assessments. We will also assess the value of genetic risk scores for disease detection and prognosis. Finally, using the rich clinical and genotype data in the UK Biobank we will analyze known targets of available therapies to determine if current medications can be repurposed for treatment of common blinding disorders.
Overall this proposal fulfils several purposes of the UK biobank: 1) the results will make it possible to improve diagnosis and prevention of age-related eye disorders by identifying individuals who are most susceptible; and 2) we will identify targets for novel therapies for these common blinding disorders that could prevent or treat disease.