Approved Research

Co-analysis of the International Mouse Phenotyping Consortium (IMPC) data and the UK Biobank exome sequencing and blood screen data to identify gene-phenotype associations

Lay summary

The UK Biobank and the International Mouse Phenotyping Consortium (IMPC) attempt to identify associations between genes and traits, that is, gene-phenotype associations. While the UK Biobank relies on genetic and phenotypic data collected for a large number of participants, the IMPC relies on phenotypes collected for mouse knockouts, that is, mice in which one gene has been knocked out (inactivated or "switched off").

Notably, an overlap in procedures to describe blood traits exists between the UK Biobank and the IMPC, involving 39 blood phenotype parameters, including white and red cell counts and biochemical data. Taking advantage of this overlap, this project will focus on associations between genes and blood traits. Our aim is to identify human genes contributing to blood molecular phenotypes by integrating IMPC and UK Biobank gene-phenotype associations.

Blood trait data has been collected for all UK Biobank participants. In terms of genetic data, in this study we plan to focus on whole-exome sequence (WES) data that has now been generated for 150,000 participants of the UK Biobank cohort. To establish associations between blood phenotypes and human genetic variants, we plan to use so-called gene-based burden methods. These methods can be used to highlight genetic variants that are likely contributing to a phenotype (or trait).

This project will highlight variants likely contributing to abnormal blood phenotypes associated with disease, and also constitutes an interesting opportunity to relate alterations in blood physiology, the immune system, enzymatic activity and blood metabolism between human and mouse, and give insight into the suitability of these mouse lines informing about human disease.