Mendelian randomization analysis of the association between vitamin B12 deficiency anaemia and the risk of developing...

The causal relationship between vitamin B12 deficiency anaemia and the risk of developing lung diseases remains unclear. This study aimed to clarify that relationship using Mendelian randomization (MR) with Bayesian weighting, focusing on pulmonary fibrosis (PF), idiopathic PF (IPF), eosinophilic asthma (EA), squamous cell lung cancer (LUSC), chronic obstructive pulmonary disease (COPD), and pulmonary embolism (PE). We analysed genome-wide association study (GWAS) data, applied five MR models with Bayesian methods to assess causality, and validated the results via sensitivity analysis. The MVMR method explores whether vitamin B12-deficient anaemia affects the pathogenesis of IPF independently of BMI. SMR was used to explore IPF-related pathogenesis, whereas a meta-analysis was used to consolidate LUSC MR findings across ethnicities. IVW analysis revealed a positive causal link between vitamin B12 deficiency anaemia status and the risk of developing PF [OR (95% CI) = 1.161 (1.021, 1.319), P = 0.023], IPF [OR (95% CI) = 1.176 (1.002, 1.380), P = 0.047 (Bayesian MR)] and EA [OR (95% CI) = 1.394 (1.084, 1.793), P = 0.010]. The results of the study demonstrate that the development of IPF is influenced by vitamin B12 deficiency independently of BMI. Conversely, vitamin B12 deficiency anaemia status was negatively associated with the development of LUSC [OR (95% CI) = 0.879 (0.760, 0.995), P = 0.001], and no causal association was detected between vitamin B12 deficiency anaemia status and the development of COPD or PE. The reverse MR analysis yielded nonsignificant results. The SMR analysis revealed a significant association between IPF onset and CUBN, a vitamin B12 target. Post-MR meta-analysis confirmed the credibility and homogeneity of these findings. Vitamin B12 deficiency anaemia is causally associated with the development of PF, IPF, and EA but is negatively associated with the development of LUSC. No causality was observed for COPD or PE. Notably, CUBN emerged as a key IPF-related gene, highlighting the intricate relationship between vitamin B12 status and pulmonary health.