Approved Research

Developing Combined Clinical and PRS Based Approaches to Predict Future Disease Burden and Develop Personalized Treatment Plans in Type 2 Diabetes

Lay summary

Scientific rationale: Diabetes is one of the most common chronic health conditions and leading causes of death. Complications and comorbidities (i.e., coronary artery disease, stroke, kidney failure, etc.) due to diabetes are also common and often severely debilitating. Indeed, diabetes is the leading cause of kidney failure, adult blindness, and lower-limb amputations (CDC 2022). Although, the course of disease is very heterogenous and there is large variability in the development of such comorbidities in diabetes patients, the current treatment approaches are far from being individualized. Mounting evidence suggests that a substantial portion of this variability is of genetic origin and a large number of regions in the genome take role, or it is polygenic. The emerging field of polygenic risk scores (PRS) takes advantage of large datasets to develop risk scores that can be used to estimate disease risk before the disease develops. While most applications of PRSs compare the genome sequences of patients to healthy individuals, its application to estimate comorbidity/complication risk in diseased persons is very limited.

Aims: Our primary aim is to develop PRS(s) that can be used for the prediction of comorbidities in diabetes patients. We postulate that such scores could be integrated into existing treatment algorithms and facilitate individualized treatment regimes. To this end, we will generate integrated risk models using various statistical tools and PRS development methods, such as single- and multi-discovery, PRS-CSx, etc.

Project duration: The project will be completed in 24 months.

Public health impact: 4.9 million people in the UK alone are diagnosed with diabetes and further 13.6 million people are at risk, together making up 27% of the UK population. Burden of diabetes (measured by "Disability-adjusted life years (DALY)") increased by 80% globally between 2000-2019 and DALY for diabetes in the UK is currently 714 per 100,000 people. Despite the epidemic level numbers, treatment of diabetes fails to take into account the interindividual differences among patients. Development of PRSs for comorbidities in type 2 diabetes patients will allow better risk management and prevention of life-threatening complications. Reduced comorbidity prevalence in diabetic patients will lower the burden on patients, families and the health system.