Genetic Evidence of Association Between Gastroesophageal Reflux Disease and Hypertensive Disorders in Pregnancy

Background: The association between gastroesophageal reflux disease (GERD) and hypertensive disorders in pregnancy (HDP) is unclear. A bidirectional Mendelian randomization (MR) analysis was conducted to investigate the causal association between GERD and HDP using the public databases. Methods: Four methods were applied in our MR analysis, including the inverse variance weighting (IVW), MR-Egger, weighted median, and weighted mode. A series of sensitivity analyses were conducted to affirm the stability and reliability of the results. Results: IVW analysis showed a potential causal association between GERD and pre-eclampsia (PE) (OR = 1.20, p = 0.048), as well as gestational hypertension (GH) (OR = 1.26, p = 0.008). The other three methods, including MR-Egger, weighted median, and weighted mode, yielded consistent results. Heterogeneity existed between GERD and PE (p < 0.05), as well as GH (p < 0.05) in sensitivity analyses. However, there was no pleiotropy in MR analysis results (p > 0.05). Leave-one-out analysis indicated that none of the SNPs had a potential impact on IVW results. In the reverse MR analysis, there is no causal effect of HDP on GERD. Conclusion: The results demonstrated that GERD exhibited a causal relationship with a high risk of HDP, which contributed to the ongoing discourse of GERD in the etiology of HDP.