Aims and objectives: Present studies showed that the association between gastroesophageal reflux disease (GERD) and asthma has not reached a conclusion. Micro-aspiration of GERD was defined as a potential factor of asthma, however, some studies yielded conflicting results. This bidirectional relation made causal inference between two diseases difficult. Thus, we performed Mendelian randomization analyses using large-scale GWAS to examine the relation between these two diseases.

Methods: A two-sample Mendelian randomization analysis was conducted using public GWAS data to investigate the genetic causal association between GERD and asthma. Outlier SNPs detected by MR-PRESSO and confounder SNPs were excluded. Causal links were mainly evaluated by the inverse variance weighted (IVW) method. Heterogeneity and sensitivity analyses were also performed to validate our findings.

Results: A history of GERD was associated with a higher risk of developing asthma (OR = 1.0032, 95%CI:  1.0015-1.0048, p = 0.00016). Pleiotropy (p = 0.11) and leave-one-out tests demonstrated that our results were robust. The heterogeneity test was statistically significant (p = 0.02), however, it did not affect the IVW results, suggesting our findings were reliable.

Conclusion: Generally, we found out that GERD could play a role in asthma development with a causal impact, which may help clinicians identify and handle patients with asthma or a higher risk of developing asthma.