Causal Associations between Immune Cell Phenotypes and Varicose Veins: A Mendelian Randomization Analysis

Area of Science:

• Immunology
• Genetics
• Vascular Biology

Background:

• Varicose veins (VVs) are a common chronic venous disorder with complex pathophysiology.
• Immune dysregulation, inflammation, and genetic factors contribute to VV development.

Purpose of the Study:

• To identify immune-related causal factors in varicose vein pathogenesis.
• Utilize Mendelian randomization (MR) to investigate immune cell phenotypes and VVs.

Main Methods:

• A 2-sample MR analysis was performed using genetic variants as instrumental variables.
• Data sourced from the Finland and genome-wide association study catalog.
• Inverse variance weighting (IVW) was the primary analysis method, with MR-Egger and weighted median for sensitivity.

Main Results:

• 79 immunophenotypes were associated with VVs, including B-cells, dendritic cells, T-cells, monocytes, myeloid cells, and regulatory T-cells (Tregs).
• Eight immunophenotypes remained significant after multiple testing correction.
• Significant associations included CD86 on myeloid dendritic cells, CD33 on myeloid cells, lymphocyte SSC-A, and CD39+ Tregs.

Conclusions:

• Immune cells play a crucial role in the pathogenesis of VVs.
• Elevated CD86 on myeloid DCs and lymphocyte SSC-A may indicate VV risk.
• CD39+ Tregs show a protective role, suggesting potential for immune modulation therapies.