Approved Research

Integrative analysis of inferred molecular traits and human phenotypic variation

Lay summary

Determining the impact of inherited and acquired DNA sequence changes on human traits can help to reveal the ways in which diseases come about. The contribution of individual changes in the DNA sequence to a trait is usually subtle and can act either by changing the biochemical functions of the gene itself or by altering the level of activity of the gene. We plan to use insights from other data collections that include gene activity levels (known as gene expression) and other types of information to help derive a better understanding of how genomic variation may contribute to variation in human traits, with a particular focus on cancer risk. DNA sequencing allows the possibility of identifying not only the inherited set of DNA variations but also the acquired changes to the genome. Using sequencing data derived from the UK Biobank cohort, this project aims to test new statistical strategies to remove artefacts that arise during DNA sequencing. These can be difficult to distinguish from acquired changes to the DNA sequence. Because the changes to the genome that are acquired by our cells throughout our lifetime can lead to diseases (particularly cancer) and are likely to have a role in aging, understanding how the number and pattern of such changes varies between people may provide insights that will help to predict and ultimately prevent disease. We expect that advances in understanding the association of genome-wide variation with human traits may contribute to cancer prevention by identifying those at greatest risk as well as contributing insights relevant for developing novel treatments for human diseases more generally. We anticipate that this work will take three years to complete.