Approved Research

Enabling discovery of genetic interactions for GWAS-informed precision therapeutics

Lay summary

Despite the fact that human genetics is accepted as a powerful tool for discovery of new medicines, there are many gaps in our understanding of the connection between genes and diseases.  This is because traditional methods of analyzing the connection imagine each gene becoming defective in isolation to give rise to disease.  The reality is that most genes work with each other synergistically in healthy people, and a defect in the way they work together is what gives rise to diseases.

We will use newly developed methods that take into account the fact that genes work together.  We will use these methods to analyze the genetic information of the many volunteers in UK Biobank who are have certain diseases versus those who do not.  The output of our efforts will be novel disease maps, which show connections between genes that contribute to each disease.  The maps will be unique to each disease.

We will then use the new methods to generate first new disease maps for metabolic diseases and cancer, then extending the methods to new disease areas including but not limited to autoimmune and neurological diseases.

These disease maps will help us design the right kinds of experiments that will lead ultimately to clinical studies in humans.  The project relies on three elements, making sure complex algorithms are working as intended (6 months), developing even faster and more sensitive algorithms (6 months), applying these algorithms to UK Biobank data (6 months), and using experiments to test the ideas that come out (12 months).