Leveraging Mendelian Randomization andGenome-wide Association Data for DrugRepurposing in Heart Failure

Abstract

Heart failure (HF) is a major global health challenge. It causes high morbidity, mortality, and economic burden.
Despite therapeutic advances, long-term outcomes remain poor, and benefits have stagnated. This drives the
search for novel, cost-effective treatments, including drug repurposing (DR). This review highlights Mendelian
randomization (MR) and genome-wide association study (GWAS) data as key tools for DR and target identification
in HF. GWAS, MR analyses, and integrative genomics datasets were used to investigate the genetics of HF and drug
targets. This GWAS-MR-based review presents evidence for repurposing GWAS-MR tools, such as Proprotein
convertase subtilisin kexin9 inhibitors, urate-lowering drugs, and lipid-modifying drugs, for HF treatment. It
also discusses how to prioritize HF drug targets and reduce confounding and reverse causality. GWAS and MR
together provide a genetically informed approach for HF therapy and target discovery. These methods can speed
up target selection and optimize precision HF treatment using suitable datasets. The author anticipates that future
advances in GWAS and MR data will further their use for DR in HF.