Polypharmacy in multiple long-term conditions: using genetics to inform a more personalised approach

Genetics and Genomics

Summary

Understanding interactions between medications and genetics could help reduce polypharmacy-driven harm by enabling safer, more personalised prescribing. We will use data from the UK Biobank, where participants have linked genetics and linked electronic medical records, to investigate how polypharmacy and genetics affect side effects and clinical outcomes.

How are we doing it?

This study will use data from the large 500,000 person UK Biobank study to assess these interactions in patients with polypharmacy.

We will:
1) Identify CYP3A4 pharmacogenetic variants by reviewing literature and PharmGKB
2) Identify UK Biobank participants prescribed multiple medications listed above
3) Ascertain clinical adverse outcomes in the linked medical records
4) Estimate associations between CYP3A4 genetic variants and adverse outcomes, using the genetic variants as instrumental variables in a Mendelian randomization framework to assess the causal relationship between CYP3A4 activity and polypharmacy-related side effects.

What happens next?

This pilot data will inform a larger external grant application (MRC project grant), focusing on pharmacogenomics in polypharmacy and reducing adverse drug interactions. Our proven track record, including the impact on clopidogrel clinical guidelines, demonstrates the potential of this approach for safer, more personalised prescribing strategies.

Funding

The MRC funded the ongoing GEMINI and TWIST grants at the University of Exeter, that laid the foundations for this NIHR BRC-funded project.

People Involved

Dr Luke Pilling, Prof Jane Masoli, Dr Deniz Türkmen.