Abstract
The aim of this study was to elucidate the causal relationship between immunophenotypes and heart failure (HF) using bidirectional Mendelian randomization (MR) analysis. Summary-level data for HF and immunophenotypes were obtained from public genome-wide association study data. Five robust MR methods were employed to delineate the causal effects between the 2. Further analyses included horizontal pleiotropic analysis, Cochran Q analysis, MR-Egger intercept test, and leave-one-out analysis. Finally, we used the screened immunophenotypes as outcomes and HF as exposure for reverse MR analyses. Eight immunophenotypes demonstrated an increased risk of HF, including immunoglobin D+ (IgD+) CD38br absolute cell (AC); double positive (CD4+CD8+) %leukocyte; CD28- CD127- CD25++ CD8br %T cell; CD28- CD127- CD25++ CD8br %CD8br; CD28+ CD45RA+ CD8br %T cell; CD19 on IgD+ CD38br; CD27 on IgD- CD38dim; CD45 on lymphocyte. Conversely, 7 immunophenotypes exhibited a reduced risk of HF, including Activated Treg AC; Im myeloid-derived suppressor cell %CD33dim human leukocyte antigen DR- (HLA DR-) CD66b-; CD33dim HLA DR+ CD11b+ %CD33dim HLA DR+; CD20 on IgD- CD38dim; side scatter-A (SSC-A) on CD14+ monocyte; SSC-A on HLA DR+ natural killer cell; CD11b on CD14+ monocyte. Importantly, we did not find any horizontal multidimensional outliers, genetic heterogeneity, directional pleiotropy, or a single nucleotide polymorphism that determines ultimate causality. The results of the reverse MR analysis were not statistically significant. In this study, the genetic correlation between 15 immunophenotypes and HF was revealed by MR analysis, which provides a reference for future clinical treatment.