Approved Research

From genetics to new drug targets: Capturing the power of genetics to support drug target identification and validation

Lay summary

Human DNA contains the genetic information that determines in part how we look, behave and age. The DNA between individuals is very variable, and these differences partly account for why some people develop diseases and others do not. So far, we have associated thousands of genetic variations in human DNA with various conditions, which have provided novel insights into their biology. Genetic variations have also been precious for drug discovery by increasing the success rate for drugs in clinical development. However, there is still a lack of effective prevention and treatment methods for many diseases, and so we urgently need to develop new therapeutics.

Genetic variations that have the most significant impact on disease development are rare, and we need large studies to investigate them. The size of the UK Biobank makes it the perfect resource to discover these variations and unveil their function and impact on disease. Additionally, using the UK Biobank resource, we can construct genetic risk scores that aggregate the effect of common variants and predict an individual's risk of developing a disease. These scores can be also used to link modifiable risk factors to diseases to provide more robust association evidence (i.e., causality).

This project aims to identify new genetic variations affecting common diseases in diverse populations and use this information in order to identify and validate new drug targets and improve disease risk prediction. In the next 3 years, we will study patterns of genetic variations, their associations with various diseases and their impact on disease risk stratification across different populations in the UK Biobank. We will also utilize genetic information to identify new modifiable risk factors for common diseases. Finally, we will complement our genetic findings with available biological information to prioritize new drug targets for clinical testing.

The project findings will broaden our understanding of common diseases, provide essential insights into the underlying biology, and may lead to new or better drug targets. In addition, we expect our findings to bring new information that can improve disease screening, diagnosis, prognosis, and treatment.