The bidirectional genetic causality between immunocyte phenotypes and dilated cardiomyopathy: A bidirectional Mendelian randomization study
TL;DR
It is indicated that CD28 on secreting regulatory T cell could mitigate the occurrence of DCM, and reciprocally, the progression of DCM could reduce the level of CD28 on secreting regulatory T cell.
Abstract
The association between immunocyte phenotypes and dilated cardiomyopathy (DCM) has been explored, however the exact pathogenesis of the relationship between immune cells and DCM is unclear. This bidirectional two-sample Mendelian randomization (MR) research aims to further validate the causal link between 731 immunocyte phenotypes and DCM. Summary statistics from a genome-wide association study data of individuals with European ancestry were utilized, including 1444 DCM cases and 353,937 controls, as well as 3757 European adults for the 731 immunocyte phenotypes. Causal effects were estimated using inverse variance weighted, MR-Egger regression, weight median estimator, weighted mode, and simple mode. Sensitivity analysis was conducted to confirm data robustness and feasibility. Based on the inverse variance weighted findings, 14 immunocyte phenotypes were risk factors for DCM (P < .05, odds ratio [OR] > 1), while 15 immunocyte phenotypes exhibited a protective effect on DCM (P < .05, OR < 1). The results of reverse MR analysis suggested evidence that DCM occurrence might elevate the levels of 17 immunocyte phenotypes (P < .05, OR > 1) and decrease the levels of 9 immunocyte phenotypes (P < .05, OR < 1). Our research indicated that CD28 on secreting regulatory T cell could mitigate the occurrence of DCM, and reciprocally, the progression of DCM could reduce the level of CD28 on secreting regulatory T cell. This study confirmed the bidirectional genetic predictive relationship between immunocyte phenotypes and DCM, underscoring the complex interplay between DCM and the immune system.