Work Strand 1 – Prediction of drug response from AIM/metabolomics in existing clinical trial multi-ethnic cohorts
Lead: Prof. Sandosh Padmanabhan (University of Glasgow)
Hypertension treatment within the UK is currently stratified according to age and self defined ethnicity (SDE). The limitations of this are well recognised, for example, a growing admixed population, differences in drug response despite stratification by age/ethnicity, etc.
We plan to use clinical trial datasets of over 8000 subjects from genotyped multi-ethnic USA cohorts (of which approximately 50% are of Black or Hispanic ethnicity) that have been randomised to various comparator drugs. In using these datasets we hope to identify genetically defined ancestry (GDA)/ ancestry information markers (AIM) that would be used to estimate the proportion of each individual’s genome comprising of European, African and Asian ancestral origin. We understand that interpretation of this data may be limited by differences in ethnic variation in vascular risk and physiology between the US and UK and by the selection of drugs used in the trails, but, it will ultimately help us investigate whether or not genetically defined ancestry (GDA) is superior to self-defined ethnicity (SDE) in predicting drug response.
We will also aim to examine the metabolomic profile of these US cohorts to determine whether or not GDA/AIM together with a metabolomics profile can be used to effectively personalise antihypertensive treatment. Finally, we will use the following predominantly white European GENRES, NORDIL and ASCOT cohorts to determine whether or not we can predict the response to antihypertensive treatment using the proof of concept genetically defined ancestry markers.