Work Strand 4
Defining mechanisms: multi-omic studies in TWINS UK cohort and SABRE
Lead: Prof. Tim Spector (King’s College London)
The Twins UK cohort is a unique cohort, representative of the general UK population, originally set up in 1992 by Prof Tim Spector, to investigate the incidence of common bone and joint disorders. The cohort has grown since then and currently comprises of around 12,000 identical and non-identical twins across the UK. This cohort spans genetic research over a range of common complex traits and is probably the most genotyped and phenotyped in the world. Over 3000 twins have undergone detailed hypertension phenotyping in which both blood pressure and other phenotypes related to vascular ageing are known to predict response to treatment. In a metabolomics screen several metabolites closely associated with arterial stiffening
This multi-omics resource is being used to combine GWAS with transcriptomics in selected tissue to find QTLs associated with metabolite signatures predictive of BP response. This has enabled Drs Cristina Menni and Ana Valdes to uncover genes whose expression correlates with the metabolites allowing to identify pathways related to BP regulation (Paper under review). The TwinsUK resource is also being used to investigate the role of a variety of compounds, such as bioactive lipids, on hypertension and to link these and other compounds to both genetic pathways and to exposures such as diet and the gut microbiome composition.
The team is exploiting the TwinsUK bioresource to uncover genes potentially mediating the response to treatment associated with individual metabolites and metabolite signatures. Pending approval, this work strand will also examine in SABRE (the largest tri-ethnic population-based cohort in the UK) the metabolite signatures in ethnic minorities with resistant hypertension.
Please see the video below to learn more about the Work Strand 4 research.