Neutrophil count and reduced risk of venous thromboembolism: a Mendelian randomization study

Abstract

ABSTRACT Background Venous thromboembolism (VTE) has a close relationship with the immune system, particularly neutrophils. This study aimed to investigate the association between blood cell traits and VTE using Mendelian randomization (MR). Method In this study, we discovered specific genetic variants associated with blood cell traits through genome-wide association studies (GWAS) conducted on 173,480 individuals of European ancestry. Additionally, we gathered summary level data on VTE from FinnGen consortium involving 377,277 individuals. To explore the connections between blood cell traits and VTE, we employed various methods, including inverse variance weighted (IVW), Mendelian Randomization-Egger (MR-Egger), weighted median, and weighted mode for comprehensive analysis, as well as Multivariable MR (MVMR) to adjust for potential confounders. Results The results of this study indicated that an elevated neutrophil count was a protective factor against VTE (odds ratio [OR] = 0.80, 95% confidence interval [CI] = 0.70–0.91, p = 1.19 × 10−3). The results were confirmed to be reliable through sensitivity analysis, which demonstrated the absence of horizontal pleiotropy, and random effects model of IVW eliminates the impact of heterogeneity. MVMR confirmed a stable causal link between neutrophil count and VTE (OR = 0.83, CI = 0.76–0.91, p = 9.97 × 10−5) after adjusting for type 2 diabetes and obesity. Conclusion According to our MR study, we found evidence suggesting that higher neutrophil count linked to a lower risk of VTE. These findings may provide potential therapeutic targets for the prevention and treatment of VTE.