心力衰竭(HF)是一种具有许多遗传和环境因素的疾病。以前的研究结果表明,免疫表型与HF有关,但是关于因果关系的研究尚无定论。因此,进行孟德尔随机化(MR)分析以确认免疫表型和HF之间的因果关系。提供遗传证据支持免疫细胞因子与HF风险的关联。
■我们根据免疫表型和全因HF的全基因组关联研究(GWAS)结果的数据选择了符合标准的工具变量。使用逆方差加权(IVW)评估731个免疫细胞因子与HF风险之间的因果关系,MR-Egger回归(MR-Egger),和加权中位数(WM)分析方法。要确定水平多效性,异质性,和遗传变异的稳定性,MR-Egger截距测试,Cochran的Q测试,MR-PRESSO,并进行留一法敏感性分析.
■MR主要方法(IVW)分析显示,共有38种免疫细胞相关因素与HF具有显着因果关系。结合三种方法的进一步分析(IVW,MR-Egger和WME)表明,六个暴露因素与心力衰竭显着相关,如下所示。树突状细胞绝对计数的影响,CD62l-CD86+髓样树突状细胞绝对计数,CD62l-CD86+髓样树突状细胞%树突状细胞,CD39+CD8+T细胞%CD8+T细胞,中央记忆CD4+T细胞CD3对心力衰竭呈阳性。然而,对于CD14+CD16+单核细胞%单核细胞观察到相反的作用。
■我们研究了免疫表型与全因HF之间的因果关系。根据结果,树突状细胞绝对计数,CD62l-CD86+髓样树突状细胞绝对计数,CD62l-CD86+髓样树突状细胞%树突状细胞,CD39+CD8+T细胞%CD8+T细胞,CD3对中央记忆CD4+T细胞加重HF,CD14+CD16+单核细胞%降低HF的风险。这些表型可以作为新的生物标志物,为全因HF的预防和治疗提供新的治疗见解。
UNASSIGNED: Heart failure (HF) is a disease with numerous genetic and environmental factors that affect it. The results of previous studies indicated that immune phenotypes are associated with HF, but there have been inconclusive studies regarding a causal relationship. Therefore, Mendelian randomization (MR) analyses were undertaken to confirm the causal connections between immune phenotypes and HF, providing genetic evidence supporting the association of immune cell factors with HF risk.
UNASSIGNED: We selected instrumental variables that met the criteria based on data from the results of genome-wide association studies (GWAS) of immune phenotype and all-cause HF. An evaluation of the causal association between 731 immune cell factors and HF risk was carried out using the inverse variance weighted (IVW), MR-Egger regression (MR-Egger), and weighted median (WM) analysis methods. To determine the horizontal pleiotropy, heterogeneity, and stability of the genetic variants, the MR-Egger intercept test, Cochran\'s Q test, MR-PRESSO, and leave-one-out sensitivity analysis were performed.
UNASSIGNED: MR principal method (IVW) analysis showed that a total of 38 immune cell-related factors were significantly causally associated with HF. Further analyses combining three methods (IVW, MR-Egger and WME) showed that six exposure factors significantly associated with heart failure, as shown below. The effect of Dendritic cell Absolute Count, CD62l- CD86+ myeloid Dendritic cell Absolute Count, CD62l- CD86+ myeloid Dendritic cell% Dendritic cell, CD39+ CD8+ T cell% CD8+ T cell, CD3 on Central Memory CD4+ T cell on heart failure was positive. Whereas, a reverse effect was observed for CD14+ CD16+ monocyte% monocyte.
UNASSIGNED: We investigated the causal relationship between immune phenotypes and all-cause HF. According to the results, Dendritic cell Absolute Count, CD62l- CD86+ myeloid Dendritic cell Absolute Count, CD62l- CD86+ myeloid Dendritic cell% Dendritic cell, CD39+ CD8+ T cell% CD8+ T cell, CD3 on Central Memory CD4+ T cell aggravate HF, and the risk of HF is decreased by CD14+ CD16+ monocyte% monocyte. These phenotypes may serve as new biomarkers, providing new therapeutic insights for the prevention and treatment of all-cause HF.