Approved Research

Identifying genetic risk factors of major complex eye diseases

Lay summary

Eye health conditions pose a global health concern, because they affect billions of people of all age groups globally. Those most affected live in underdeveloped and developing countries and often suffer visual disabilities even from causes that are preventable. Complex eye diseases (CEDs) are caused by a combination of genetic and environmental factors. Early diagnosis and treatment of CEDs is essential to minimize or prevent vision loss globally. CEDs tend to disproportionately affect individuals ethnic minority backgrounds, such as those of African and other ancestries, due to a combination of ethnicity-specific higher genetic predisposition and social factors limiting timely access to healthcare.

Here we propose to develop complex eye genetic disease risk prediction tools based upon polygenic risk scoring method. These tools are intended to help predict the likelihood of developing CEDs like glaucoma and age-related macular degeneration early in the course of the disease in individual of ethnically diverse backgrounds. The goal of this research project is to develop, and clinically validate polygenic risk scores (PRS) for CEDs taking advantage of the information available in the UK Biobank data. We aim to analyze the genetic information of all UK Biobank participants, using direct measurements, questionnaire and hospital episode data. This will allow us to determine trans-ethnic genetic determinants of CEDs, using markers whose effects are shared across various independent cohorts and ethnicities.

We intend to validate the published associations between various genetic variants and CED traits in various ethnic groups and perform extended analysis over the long term to discover new associations in these populations. The initial phase of our work will last for 2-3 years, during which we will implement models incorporating existing genetic knowledge and another year to improve the number of predictive value of known markers statistically associated to complex eye disease. As this is a fast progressing field, we are aware of the possibility that this project may have to be extended to keep the pace of other discoveries and crosscutting lines of investigation that could help improve genetic prediction in our societies.