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:
- Proteins: We have measured thousands of plasma proteins in subsets of participants from the INTERVAL Bioresource using platforms such as the Olink Target and Explore assays, the SomaLogic SomaScan assay and other multiplex protein assays. By running genomewide association studies (GWAS) on these proteins, we are creating ‘genomic atlases’ of the human plasma proteome, which can then be used to assess the likely causality of proteins and pathways in relation to cardiovascular diseases, as well as many other diseases. For example, in 2018, we published a GWAS of ~3500 proteins in ~3200 participants from the INTERVAL Bioresource, identifying nearly 2000 associations (Sun et al, Nature, 2018). Further details, including access to GWAS summary statistics and individual-level data from our publications, can be found on our proteins page.
- Lipids and metabolites: We have used multiple high-dimensional ‘omics assays that in total capture information on ~3000 distinct lipids, lipoprotein classes and metabolites in up to 150,000 participants. For example, we have used Metabolon’s Discovery HD4 untargted mass spectrometry platform to quantify ~1000 plasma metabolites in ~17,000 participants from the INTERVAL Bioresource. We have analysed these data with respect to imputed array data and also whole-exome and whole-genome sequencing data, in collaboration with the Wellcome Sanger Institute and MRC Epidemiology Unit.
- 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. Further details, including access to GWAS summary statistics from our publications, can be found on our haematological traits page.
- 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.