Multimorbidity Mechanism and Therapeutics Research Collaborative

Lead Research Organisation: University College London
Department Name: Institute of Cardiovascular Science

Abstract

As people live to a greater age there is an increased risk of suffering more than one health condition at a time. Known as multimorbidity this has a serious effect on the daily lives of patients, their families and their carers. The project will examine the sequence and patterns of multimorbidity and the evidence obtained will aid both the prediction and treatment of patients with multiple health conditions. We will also seek to address the problem of coordinating treatments so that treatment for one condition does not cause difficulties in the treatment of another condition suffered by the same patient. The frequency of this "competition" between health conditions will be established and solutions identified. In doing this we hope to identify medicines that are able to treat more than one condition and investigate the potential of new uses for existing safe medicines.
Our research will utilise anonymous patient data recorded by the NHS as well as the findings from existing genetic studies and clinical trials. We will look across the different types of evidence to check consistency to ensure our recommendations are sound. Where uncertainties remain we will recommend new clinical trials or genetic studies. In this way we hope to improve the outlook for patients, regardless of their particular combination of health conditions, by maximising the benefits from effective treatments.
Two patient participants are co-applicants on this project. A Patient and Public Advisory Group will be established which will also assist in ensuring that the findings from the project are widely disseminated. During the course of our work we will liaise with organisations such as the Coalition for Collaborative Care with a view to the establishment of a national Multimorbidity Special Interest Group.

Technical Summary

Our research will uncover mechanisms underlying multimorbidity by triangulating relationships between medicines, drug targets and disease outcomes from electronic health records (EHRs), genetic association studies and trials. The findings will maximise treatment benefits by guiding drug indication expansion and re-purposing; reduce harm by optimising prescribing when diseases co-exist; and yield new tools for prediction and prevention of multi-morbidity.
 
Title Should you donate your DNA to cure diseases? 
Description TED Ed animation with Greg Foot 
Type Of Art Film/Video/Animation 
Year Produced 2021 
Impact 158,000 you tube views 
 
Description University College London Biomedical Research Centre
Amount £90,186,915 (GBP)
Funding ID NIHR203328 
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 12/2022 
End 11/2027
 
Description Welcome Trust Collaborative Award 'Prediction of complications of diabetes mellitus utilising novel retinal image analysis, genetics, and linked electronic health records data.'
Amount £1,126,103 (GBP)
Funding ID 224390/Z/21/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2022 
End 03/2026
 
Title Look up tool based on analyses of disease co-occurrence from Identifying and visualising multimorbidity and comorbidity patterns in patients in the English National Health Service: a population-based study published in Lancet Digital Health 2023 
Description An R shiny app to visualise and quantify multimorbidity and comorbidity frequencies and networks. 
Type Of Material Improvements to research infrastructure 
Year Produced 2023 
Provided To Others? Yes  
Impact 2 citations - 1 featuring the paper in Cell Reports Medicine 6 news mentions 112 social media 3 - wikipedia references -"Electronic health record', 'Global health', '2022 in science' 
URL https://multimorbidity.caliberresearch.org/
 
Title Look up tool based on summary statistics from Mapping the proteo-genomic convergence of human diseases paper in Science. 2021 Nov 12; 374(6569): eabj1541. 
Description A tool to identify protein disease associations through genome wide colocalisation analysis. 
Type Of Material Improvements to research infrastructure 
Year Produced 2021 
Provided To Others? Yes  
Impact 23,000 downloads of the paper 23 citations 
URL https://pubmed.ncbi.nlm.nih.gov/34648354/
 
Title Mapping the proteogenomic convergence of human disease search tool 
Description A tool to visualise gene and protein relationships across multiple diseases. 
Type Of Material Model of mechanisms or symptoms - human 
Year Produced 2021 
Provided To Others? Yes  
Impact Widespread interest from the science community and general audience. Altmetric score 520. 
URL https://www.science.org/doi/10.1126/science.abj1541
 
Title Derivation of relevant metrics to assess the performance of polygenic risk scores from reported metrics. 
Description Secondary analysis of the PGS Catalog. 
Type Of Material Data analysis technique 
Year Produced 2022 
Provided To Others? Yes  
Impact Awaited 
 
Description Collaboration with Bristol, Birmingham, Liverpool, and Cambridge as part of the Multimorbidity Mechanism and Therapeutics Research Collaborative 
Organisation University Hospitals Birmingham NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution Led the application for funding and coordination of the award
Collaborator Contribution Topic specific expertise
Impact Detailed elsewhere
Start Year 2021
 
Description Collaboration with Bristol, Birmingham, Liverpool, and Cambridge as part of the Multimorbidity Mechanism and Therapeutics Research Collaborative 
Organisation University of Bristol
Country United Kingdom 
Sector Academic/University 
PI Contribution Led the application to UKRI for the award. Co-ordinate the collaborative
Collaborator Contribution Contribution to specific work packages and interdisciplinary working.
Impact Publications listed elsewhere
Start Year 2021
 
Description Collaboration with Exeter in an application to UKRI for a clinical community of practice grant 
Organisation University of Exeter
Country United Kingdom 
Sector Academic/University 
PI Contribution Support of the MMTRC
Collaborator Contribution Leading the application
Impact None yet
Start Year 2022
 
Description Collaboration with Leicester in an application to UKRI for funding for a community of practice grant in statistical genetics 
Organisation University of Leicester
Country United Kingdom 
Sector Academic/University 
PI Contribution One of the ECRs in the MMTRC collaborative is a co-applicant
Collaborator Contribution Leicester are leading
Impact None yet
Start Year 2022
 
Description Collaboration with Professor Nick Wald and Joan Morris 
Organisation St George's University of London
Country United Kingdom 
Sector Academic/University 
PI Contribution Developed the idea of converting reported metrics on performance of polygenic scores into metrics most relevant for prediction
Collaborator Contribution Developed the underlying statistical methods
Impact Pre print in MedRxiv Paper under review in Communications Medicine
Start Year 2021
 
Description Collaboration with University Medical Centre Amsterdam 
Organisation Amsterdam Medical Center
Country Netherlands 
Sector Hospitals 
PI Contribution Joint scientific meeting in September 2023 to plan academic collaboration.
Collaborator Contribution All members of the Amsterdam research group attended, gave presentations and participated in the collaboration planning workshops.
Impact Multidisciplinary - genomics, imaging data science, clinical science, epidemiology.
Start Year 2023
 
Description Patient group workshop on polypharmacy 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Patients, carers and/or patient groups
Results and Impact The workshop involved presentations on prescribing and polypharmacy researchers involved in the MMTRC to the Patient Involvement in Multimorbidity Group established as part of the award.
Presentations were followed by question and answer sessions and contributed to shaping plans for future research.
Year(s) Of Engagement Activity 2023