The Causal Relationship between Blood Cell Traits and Valvular Heart Disease: A Two-Sample Mendelian Randomization Study

Abstract

Background

The pathogenesis of valvular heart disease (VHD) remains unclear, highlighting the need for further research on risk factors.

Objectives

To explore the potential causal links between blood cell traits and four types of VHD: rheumatic heart disease, mitral valve disease, aortic valve disease, and tricuspid valve disease.

Methods

This study utilized summary statistics from large-scale GWAS and a two-sample Mendelian randomization approach, analyzing thirteen blood cell traits as exposures and four VHD phenotypes as outcomes. The primary MR method was inverse-variance weighted (IVW), supplemented by MR-Egger, weighted median, and weighted mode methods, with extensive sensitivity analyses to verify result reliability, where a p value < 0.05 was considered statistically significant.

Results

Among the thirteen blood cell traits examined, neutrophil count displayed a positive causal association with mitral valve disease (OR = 1.46, 95% CI: 1.16-1.85, p < 0.001) using the IVW method. This finding was further corroborated by the MR-Egger method (OR = 1.73, 95% CI: 1.09-2.75, p = 0.02), strengthening the evidence for this causal relationship. For this analysis, 253 robust genetic variants were used as instrumental variables. Additionally, mean corpuscular volume (MCV) showed a negative causal association with tricuspid valve disease (OR = 0.65, 95% CI: 0.44-0.96, p = 0.03) using the IVW method, based on 268 instrumental variables. Other blood cell traits did not show significant causal relationships with VHD. A comprehensive sensitivity analysis supported the robustness of our results.

Conclusions

The findings of this study suggest potential causal involvement of neutrophil count and MCV in the development of mitral valve disease and tricuspid valve disease, respectively.