The Application of Mendelian Randomization in Cardiovascular Disease Risk Prediction: Current Status and Future Prospects

Cardiovascular disease (CVD), a leading cause of death and disability worldwide, and is associated with a wide range of risk factors, and genetically associated conditions. While many CVDs are preventable and early detection alongside treatment can significantly mitigate complication risks, current prediction models for CVDs need enhancements for better accuracy. Mendelian randomization (MR) offers a novel approach for estimating the causal relationship between exposure and outcome by using genetic variation in quasi-experimental data. This method minimizes the impact of confounding variables by leveraging the random allocation of genes during gamete formation, thereby facilitating the integration of new predictors into risk prediction models to refine the accuracy of prediction. In this review, we delve into the theory behind MR, as well as the strengths, applications, and limitations behind this emerging technology. A particular focus will be placed on MR application to CVD, and integration into CVD prediction frameworks. We conclude by discussing the inclusion of various populations and by offering insights into potential areas for future research and refinement.