Investigating the causal association between heme oxygenase-1 and asthma: A bidirectional two-sample Mendelian randomization analysis in a European population.

Background: The association between heme oxygenase-1 (HO-1) and asthma has been a subject of debate in both observational and experimental studies. We aimed to evaluate the potential causal relationship between HO-1 and asthma. Materials and methods: A bidirectional two-sample Mendelian randomization (TSMR) study was conducted to examine the causal relationship between HO-1 and asthma. In the forward Mendelian randomization (MR) analyses, HO-1 was considered as the exposure, while asthma as the outcome. Conversely, in the reverse MR analyses, asthma was regarded as the exposure, and HO-1 as the outcome. Data for HO-1 and asthma were obtained from publicly accessible genome-wide association studies (GWAS). These causal relationships were identified through 5 MR methods, namely MR-Egger, weighted median, inverse-variance weighted (IVW), simple mode, and weighted mode. Additionally, sensitivity tests were conducted to assess the robustness of MR study. Finally, additional asthma datasets and childhood asthma were selected to validate the findings. Results: In the forward MR analyses, according to the IVW method, genetically predicted HO-1 displays a negative correlation with the risk of asthma (OR 0.947, 95% CI 0.905-0.990). It was not found any SNP overly sensitive or disproportionately responsible for the outcome. No evidence of heterogeneity and pleiotropy between SNPs was observed. Genetically predicted asthma was not associated with HO-1 in reverse MR analyses using the IVW method. The same results were validated in additional asthma datasets and in childhood asthma. Conclusion: The results of MR analysis revealed heme oxygenase-1 as a protective factor for asthma.