Yang Zhenyu, Li Jixin, Liu Fengzhao, Xiu Xiaohan, Zhong Weibo, Sun Zhigang, Zhu Xinyu, Chen Mengzhu, Chen Xihao, Zheng Haohong, Guo Dandan
The Second Clinical Medical College of Heilongjiang University of Chinese Medicine, Harbin, China.
Department of Acupuncture, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Medicine (Baltimore). 2025 May 23;104(21):e42530. doi: 10.1097/MD.0000000000042530.
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.
本研究的目的是使用双向孟德尔随机化（MR）分析阐明免疫表型与心力衰竭（HF）之间的因果关系。HF和免疫表型的汇总水平数据来自公开的全基因组关联研究数据。采用五种稳健的MR方法来描述两者之间的因果效应。进一步的分析包括水平多效性分析、 Cochr an Q分析、MR-Egger截距检验和留一法分析。最后，我们将筛选出的免疫表型作为结局，HF作为暴露因素进行反向MR分析。八种免疫表型显示HF风险增加，包括免疫球蛋白D+（IgD+）CD38br绝对细胞（AC）；双阳性（CD4+CD8+）%白细胞；CD28-CD127-CD25++CD8br %T细胞；CD28-CD127-CD25++CD8br %CD8br；CD28+CD45RA+CD8br %T细胞；IgD+CD38br上的CD19；IgD-CD38dim上的CD27；淋巴细胞上的CD45。相反，七种免疫表型显示HF风险降低，包括活化调节性T细胞AC；免疫髓系来源抑制细胞%CD33dim人类白细胞抗原DR-（HLA DR-）CD66b-；CD33dim HLA DR+CD11b+%CD33dim HLA DR+；IgD-CD38dim上的CD20；CD14+单核细胞上的侧向散射A（SSC-A）；HLA DR+自然杀伤细胞上的SSC-A；CD14+单核细胞上的CD11b。重要的是，我们未发现任何水平多维异常值、遗传异质性、定向多效性或决定最终因果关系的单核苷酸多态性。反向MR分析结果无统计学意义。本研究通过MR分析揭示了15种免疫表型与HF之间的遗传相关性，为未来临床治疗提供了参考。
