Causal relationships between blood cell perturbation responses, immune cell phenotypes, and cardiomyopathy: A two-sample Mendelian randomization and mediation analysis

Clinical investigations have demonstrated that blood and immune cells are involved in the pathophysiological processes of dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). However, the causal relationships between these cellular components and the development of DCM and HCM remain uncertain. A two-sample Mendelian randomization analysis was performed to evaluate the causal effects of blood cells and immune cells on DCM and HCM. The primary analytical method was inverse variance weighting, supplemented by Mendelian randomization-Egger, weighted median, and MR-PRESSO approaches. Furthermore, immune cells were examined as mediators to assess their intermediary roles in the causal pathways linking blood cells with DCM and HCM. Significant causal associations were observed between red blood cells, monocytes, eosinophils, and platelets and DCM and HCM ( P < .05). CD127 on CD8br, naive CD8br %CD8br, CD16− CD56 on natural killer cell, CD45 on T cell, and lymphocyte AC were identified as mediators in the causal pathways connecting various blood cell types to DCM and HCM. This study provides robust evidence for the causal roles of specific blood cell and immune cell phenotypes in the development of DCM and HCM. These findings open new avenues for investigating the hematological immune system in cardiomyopathy and present novel opportunities for therapeutic interventions targeting DCM and HCM.