(MRC DTP) Translating genetic discoveries to improve the accuracy of predicting cardiovascular outcomes in patients with rheumatic musculoskeletal diseases
About the Project
The accurate estimation of an individual’s risk of cardiovascular disease (CVD) is essential for timely intervention with preventative treatments. However, current screening tools used to estimate CVD risk in the general population, such as QRISK3, are inaccurate in individuals with chronic inflammatory conditions, such as rheumatic musculoskeletal diseases (RMDs). This inadequacy leads to a significant health inequality and epidemiological show that patients with rheumatoid arthritis (RA) have increased CVD-related mortality compared to the general population, which is particularly high in younger age groups and women. In particular, coronary artery disease (CAD), driven by atherosclerosis, often develops in RA patients up to 10 years earlier than in the general population.
The risk factors for CAD in the general population are well established, but they do not fully account for the heightened CAD risk in patients with RA where disease-related factors, such as systemic inflammation, also play a critical role. Moreover, individual traditional risk factors behave differently in RA patients. For example, male sex and age confer less risk in this patient group.
The differing contributions of traditional and disease-related risk factors have significant implications for the use of CAD screening tools which are calibrated for the general population. These screening tools are known to be inaccurate in patients with RA which highlights the need for RA-specific risk models that incorporate both traditional and disease-related factors to better estimate risk.
One such approach may be the use of polygenic risk scores (PRS) which measures an individual’s inherited risk to a complex disease, such as CAD, based on the aggregation of many genetic variants. These approaches are now showing promise for CAD risk prediction in the general population and are progressing towards clinical utility with studies, and clinical trials, investigating the benefit of integrating PRS with existing screening tools to create what is referred to as an integrated risk tool (IRT).
As PRS gain acceptance for use in the general population, we believe it is essential to evaluate the performance of PRS-based screening tools in patients with RMDs to prevent an increase of existing healthcare disparities. This PhD project focuses on developing and validating new methods for the early detection of CVD specifically tailored to patients with RMDs by combing genetic and health data science approaches. By enhancing early detection, we aim to improve preventative care and ultimately reduce CVD incidence in this high-risk population.
https://www.musculoskeletal.manchester.ac.uk/
http://www.cfgg.manchester.ac.uk/
Eligibility
Applicants must have obtained or be about to obtain a minimum Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline.
Before you Apply
Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.
How to Apply
To be considered for this project you MUST submit a formal online application form – on the application form you must select MRC DTP PhD Programme. If you select the incorrect programme your application cannot be considered. Full details on how to apply can be found on the MRC DTP website.
Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered. If you have any queries regarding making an application, please contact our admissions team.
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.
Funding Notes
Studentship funding is for 4 years and covers tuition fees and an annual stipend. This does not include any costs associated with relocation.
Open Days
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