The CEU is identifying and selecting ‘omics assays that focus on traits in types of biological domains for which some causal CVD risk factors have already been established, thereby increasing the likelihood of identifying additional causal risk factors after a detailed ‘omics investigation in those domains.
The CEU focuses on traits in types of biological domains for which some causal CVD risk factors have already been established. Our current priority areas are:
- Blood pressure: Using the CHD Exome+ Consortium, the CEU identified 31 novel blood pressure loci, including some of the first rare coding variants of strong effect to be identified (Surendran, Nat Genet 2016;38:1151-61). We have also contributed to the discovery of a further 41 blood pressure loci, several of which highlight tissues beyond the classical renal system in blood pressure regulation. We plan to extend this work by including hundreds of thousands of additional participants from the UK Biobank study.
- Haematological traits: The CEU has provided co-leadership for the discovery of ~2400 novel genetic variants associated with volumes, counts and other phenotypes of circulating red cells, white cells and platelets (Astle et al, Cell, 2016). We are extending this work to novel functional cell parameters and iron biomarkers.
- Lipids and metabolism: We are assaying multiple high-dimensional ‘omics assays that in total capture information on ~3000 distinct lipids, lipoprotein classes and metabolites in up to 150,000 participants. We are analysing these with respect to imputed array data and also whole-exome and whole-genome sequencing data from the INTERVAL bioresource, in collaboration with the Wellcome Trust Sanger Institute and MRC Epidemiology Unit.
- Proteins: We have measured more than 3500 unique plasma proteins in subsets of participants from the INTERVAL bioresource. By running genomewide association studies on these proteins we created a ‘genomic atlas’ of the human plasma proteome, which we used to assess the likely causality of proteins and pathways in relation to cardiovascular diseases, as well as many other diseases (Sun et al, Nature, 2018).