Metabolomics approaches to understanding the excess risk of cardiovascular disease in rheumatoid arthritis

Cardiovascular disease (CVD) is a major comorbidity and leading cause of death in patients with rheumatoid arthritis (RA) (1). Traditional CVD risk factors (e.g. smoking, high blood pressure) play an important role in RA but do not account for all the risk, with approximately 30% risk resulting from RA-related factors and associated systemic inflammation (2). Analysis of small-molecule metabolites in the blood of patients with CVD has identified a number of key pathways linking systemic inflammation to disease risk (3). However, the molecular mechanisms underpinning these associations or their relevance to CVD in RA has not been fully investigated.

This studentship will apply state-of-the-art statistical techniques to identify small-molecule metabolite risk factors for CVD in RA, characterise the role of metabolites in determining important RA outcomes and identify the key molecular pathways to facilitate new mechanistic understanding, enhance patient monitoring and identify new targets for treatments.

The association between small-molecule metabolites and pre/sub-clinical CVD will be investigated using linear regression methods in the CADERA (Coronary Artery Disease Evaluation in Rheumatoid Arthritis) trial dataset where multi-parametric cardiac magnetic resonance data are already generated (4). Logistic regression based methods will be used to correlate metabolite levels with CVD and RA prevalence using large public databases (e.g. UK Biobank). Cox regression analysis will be used to assess the influence of metabolite biomarkers on CVD mortality in a large in-house prospective observational cohort of RA patients. Finally, genetic analysis will identify metabolite quantitative trait loci to assess genetic risk scores for prioritised metabolite biomarkers of CVD in RA.

1. Young A, et al. Rheumatology (Oxford) 2007;46(2):350–7.

2. Crowson CS, et al. Ann Rheum Dis 2018;77(1):48–54.

3. Ilioufi A, et al. Heart 2021;0:1–7.

4. Plein S, et al. Ann Rheum Dis 2020; 79(11):1414-1422.

Entry Requirements

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area/subject. Candidates with previous laboratory experience are particularly encouraged to apply.

How To Apply

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the appropriate subject title.

For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences.

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/”