Approved Research

Developing and validating risk prediction methods for complex traits

Lay summary

Genetic testing is widely used to diagnose monogenic diseases, caused by changes in a single gene.  However, many diseases are polygenic, that is they are influenced by a large number of genetic variants scattered throughout the genome. Polygenic risk scores combine the effects of hundreds or thousands of such risk variants to determine a risk score associated with how an individual's risk of a particular disease compares to others in a population, and may also be combined with environmental factors. Polygenic risk scores are starting to enter clinical application, however, improving performance, applicability to diverse ancestries, robustness, integration with rare variants and non-genetic factors, are all areas of active research.

Seonix Bio has already developed a polygenic risk score for Primary Open Angle Glaucoma (POAG), a leading cause of irreversible blindness worldwide, which affects 2-3% of the population over age 40. This enables those at higher risk to be identified sooner, so any glaucoma can be treated sooner, and sight can be saved.

Seonix is now similarly developing a suite of risk scores and other methods to understand and predict a wide range of ocular (e.g. age-related macular degeneration) and non-ocular diseases and complex traits (e.g. cancer).

Seonix seeks to use UK Biobank data to discover, improve and further validate risk prediction algorithms for glaucoma and other complex traits, in diverse ancestries, as well as incorporating other genetic factors (e.g. rare genetic variants) and other non-genetic risk data (e.g. clinical characteristics like age, family history, and clinical examination data). 

The UK Biobank database is a powerful resource containing genetic and detailed clinical information on half a million individuals, thus offering us an unrivalled opportunity to develop, validate and refine our methods.

Our research will lead to clinical validation of risk assessment approaches for a range of complex traits, as well as development of methods for risk prediction. The project has a strong clinical translation focus. We anticipate the products and services we develop will lead to improved management of patient health through a better understanding of disease risk, prognosis and treatment options. We believe publications resulting from the project will add to the literature on clinical validation and implementation of polygenic risk scores.