Genetic variation, adipokines, and cardiometabolic disease

• Genome-wide association studies have identified multiple genetic variants associated with circulating levels of adipokines. • There is limited genetic proof of causal relationships between adipokines and cardiometabolic disease. • Incorporation of genetic evidence is important for improving the success rate of adipokine-based drug candidates. Adipokines are adipocyte-secreted cell signalling proteins that travel to distant target organs and tissues, where they regulate a variety of biological actions implicated in cardiometabolic health. In the past decade, genome-wide association studies have identified multiple genetic variants associated with circulating levels of adipokines, providing new instruments for examining the role of adipokines in cardiometabolic pathologies. Currently, there is limited genetic evidence of causal relationships between adipokines and cardiometabolic disease, which is consistent with findings from randomized clinical trials that have thus far shown limited success for adipokine-based treatments in improving cardiometabolic health. Incorporating human genetic data in early phases of target selection is essential for enhancing the success of adipokine-based therapies for cardiometabolic disease.