Complex diseases including cardiovascular disease (CVD) and pain tend to be affected by multiple factors. It has been demonstrated that genetic and non-genetic factors synergistically determine the development of these diseases. Genetic factors describe an individual’s baseline risk for diseases. Polygenetic risk score (PRS) is aggregate information for significant genetic variants calculated from relevant genome-wide association studies (GWAS) and is a powerful tool to stratify an individual’s genetic risk. At the same time, non-genetic risk factors (e. g., physiological state, social and environmental factors) have been demonstrated to be associated with CAD and pain. However, the prospective predictive value of multiple non-genetic factors in comparison with PRS has not been thoroughly examined.
In this project, we aim to 1) construct and update the PRS using the existing largest GWAS on CVD and pain, suppose it can explain a more fraction of these diseases; 2) examine the predictive ability of the non-genetic exposures for CVD and pain using factors recorded in the UK Biobank; 3) test the complementary value of the composite non-genetic exposures to the PRS for CVD and pain.
The project is expected to last 3 years. The evidence between non-genetic risk factors and genetic predisposition will contribute to finding the meaningful factors which prevent and predict the development of CVD and pain and facilitate more personalized strategies. The outcome of this project will support population-level preventive and predictive services and resolve the burden cost of CVD and pain.