Exploring the causal relationship between immune cell and all-cause heart failure: a Mendelian randomization study

Area of Science:

• Immunology
• Cardiovascular Genetics
• Statistical Genetics

Background:

• Heart failure (HF) is influenced by genetic and environmental factors.
• Previous studies suggest associations between immune phenotypes and HF, but causal links remain unclear.
• Immune cell factors may play a role in HF pathogenesis.

Purpose of the Study:

• To investigate the causal relationship between immune phenotypes and all-cause heart failure (HF).
• To provide genetic evidence for the association of immune cell factors with HF risk using Mendelian randomization (MR).
• To identify potential immune biomarkers for HF prevention and treatment.

Main Methods:

• Utilized genome-wide association study (GWAS) data for immune phenotypes and all-cause HF.
• Employed Mendelian randomization (MR) analyses, including inverse variance weighted (IVW), MR-Egger, and weighted median (WM) methods.
• Performed sensitivity analyses (MR-Egger intercept, Cochran's Q, MR-PRESSO, leave-one-out) to assess pleiotropy, heterogeneity, and stability.

Main Results:

• MR analysis identified 38 immune cell-related factors significantly associated with HF.
• Six factors showed significant causal associations with HF across multiple MR methods.
• Increased risk of HF was associated with higher counts/percentages of Dendritic cell Absolute Count, CD62l- CD86+ myeloid Dendritic cell, CD39+ CD8+ T cell, and CD3 on Central Memory CD4+ T cell.
• Decreased HF risk was associated with CD14+ CD16+ monocyte percentage.

Conclusions:

• Specific immune cell phenotypes, including dendritic cells, certain T cells, and monocytes, have a causal impact on heart failure risk.
• These identified immune factors may serve as novel biomarkers for HF.
• Findings offer potential new therapeutic targets for the prevention and treatment of heart failure.