The relationship between pulmonary ventilation function and bone marrow hematopoietic function: A mendelian randomization analysis

Ariticle ID: 274

Abstract

Background: In recent years, the comorbidity between respiratory and hematopoietic system diseases has emerged as a new challenge. However, the potential genetic link between the ventilatory function of the respiratory system and the hematopoietic function of the bone marrow remains unclear. In this study, we conducted a comprehensive investigation into the possible genetic connection between lung ventilatory function and bone marrow hematopoietic function. Methods: We selected two exposure factors, Forced Expiratory Volume in 1 second (FEV1) and Forced Vital Capacity (FVC), which represent pulmonary ventilation function, and two outcome indicators, Immature Fraction of Reticulocytes (IFR) and Reticulocyte Count (RC), which represent bone marrow hematopoiesis function, from published genome-wide association studies. Based on the three core assumptions of Mendelian randomization analysis, we extracted Single Nucleotide Polymorphism (SNPs) associated with FEV1 and FVC as instrumental variables for the exposure factors. We then conducted two-sample Mendelian randomization analyses using inverse variance weighted (IVW), weighted median, and MR-Egger regression methods. Lastly, we assessed the reliability of the testing results through MR-Egger, Cochran’s Q test, and the leave-one-out test. Through these steps, we aimed to explore the causal relationship between pulmonary ventilation function and the outcome of bone marrow hematopoiesis function and evaluated the reliability of the testing results using methods such as MR-Egger, Cochran’s Q test, and the leave-one-out test. Results: The IVW method revealed that a decrease in FEV1 is associated with an increase in IFR (β = −0.072, 95% CI: −0.131 to −0.014, p = 0.01), and the results from MR-Egger regression showed a similar association (β = −0.169, 95% CI: −0.342 to −0.004, p = 0.05). Furthermore, a decrease in FEV1 is associated with an increase in RC (β = −0.143, 95% CI: −0.198 to −0.087, p =4.00E-07), and MR-Egger regression yielded consistent results (β = −0.216, 95% CI: −0.381 to −0.541, p=1.07E-02). Similarly, a decrease in FVC is associated with an increase in IFR (β = −0.073, 95% CI: −0.116 to −0.031, p = 6.17E-04), and MR-Egger regression showed a similar trend (β = −0.046, 95% CI: −0.160 to −0.067, p=0.42). Additionally, a decrease in FVC is associated with an increase in RC (β = −0.173, 95% CI: −0.221 to −0.125, p = 2.33E-12), and MR-Egger regression yielded consistent results (β = −0.142, 95% CI: −0.272 to −0.012, p = 3.32E-02). The reliability tests indicated heterogeneity in the above MR analyses but no evidence of horizontal pleiotropy. Therefore, a fixed-effect model IVW was used to explore the causal relationships, which were found to be robust and reliable with no outliers or significant bias in this study. Conclusion: This study indicates that there is a negative causal relationship between pulmonary ventilation function and bone marrow hematopoietic function. A decrease in pulmonary ventilation function stimulates bone marrow hematopoiesis. However, further research is needed to elucidate this mechanism.