Arquivos brasileiros de cardiologia · 2026
The Causal Relationship between Blood Cell Traits and Valvular Heart Disease: A Two-Sample Mendelian Randomization Study.
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Wu Xiaoli, Li Yufeng, Tian Jinyu
Аннотация
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.
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.