Genetic evidence prioritizes circulating proteins for heart failure beyond shared BMI-related genetic liability

The study examined genetic factors associated with heart failure (HF) independently of genetic factors related to body mass index (BMI). Using advanced genetic analyses, researchers identified nine circulating proteins associated with heart failure that are not linked to shared genetic liability with BMI. Among the identified proteins were CELSR2, whose higher levels were associated with lower heart failure risk (odds ratio 0.96), and CSF3, whose higher levels were associated with higher risk of nonischemic heart failure (odds ratio 1.32). Some of these proteins, such as CELSR2 and TMEM106B, were localized in failing left ventricular myocardium. These findings expand understanding of genetic mechanisms in heart failure and identify new proteins for further research and potential drug development.