Approved Research

Propagation of genetic effects from DNA to complex traits via molecular and cellular phenotypes

Lay summary

Small genetic differences between individuals in a population lead to millions of 'natural experiments' that can be used to understand the biological processes that play a role in both health and disease. However, these natural experiments are often difficult to interpret, because genetic variants are associated with many different genes and traits simultaneously. As a result, identifying which genes causally influences which human traits and diseases has remained challenging. Recent developments in statistical methodology have made it possible to better disentangle the results of these natural experiments. We plan to apply these novel statistical methods to a number of molecular and cellular measurements from the UK Biobank and integrate the results with the gene and protein data that we have previously curated as part of the eQTL Catalogue project. In addition to improving our understanding of the fundamental principles of how genetic variants influence various aspects of human biology, we believe that our results will also improve future drug discovery efforts by helping both academic as well as industry researchers to better distinguish genes that cause a trait or disease from those that are merely associated with it. The project is scheduled to take approximately three years to complete.