In this project, we plan to use the extensive phenotype and genetic data within the UK Biobank to investigate the effects of various drug combinations across a broad disease spectrum. As the global prevalence of chronic diseases continues to rise, more patients are prescribed combinations of two or more drug classes, such as antihypertensives, antidiabetics, lipid-lowering agents, and so on. Although current clinical guidelines support the coadministration of these medications, their drug-drug interactions and the long-term health outcomes of combination therapy remain insufficiently evaluated. However, conducting new randomized control trials (RCTs) to compare combination therapies with monotherapy or alternative combinations would require substantial financial investment and time commitment.
Mendelian randomization (MR) framework uses genetic variants as instruments, which are naturally randomized at conception. An extension of this framework, drug-target MR, has demonstrated its capacity to provide estimates comparable to those obtained from RCTs for evaluating drug efficacy and safety. Previous phenome scans conducted using antihypertensive monotherapy drug-target MR not only confirmed established associations but also revealed potential side effects that had not been reported. Additionally, factorial MR has been proposed to explore the interactions between two exposures, such as dual pharmacological interventions.
This study aims to investigate the effects of commonly prescribed drug combinations on the risk of a wide range of diseases, providing valuable insights into the potential benefits and risks associated with combination therapy.
