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

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.

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.

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.

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.