Gastroesophageal Reflux Disease and Preterm Birth: Univariate and Multivariate Mendelian Randomization

Abstract

Xinyu Han,1 Tian Qiang Wu,1 Ruiting Yao,1 Chang Liu,1 Lu Chen,2 Xiaoling Feng2 1Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, People’s Republic of China; 2Department of Gynecology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, People’s Republic of ChinaCorrespondence: Xiaoling Feng, Department of Gynecology, The First Affiliated Hospital of Heilongjiang University, No. 26, Heping Road, Xiang-Fang District, Harbin City, Heilongjiang Province, People’s Republic of China, Email [email protected]: Observational studies have established a connection between Gastroesophageal reflux disease (GERD) and preterm birth (PTB). Nevertheless, these correlations can be affected by residual confounding or reverse causality, resulting in ambiguity regarding the connection. The objective of this study was to assess the relationship between genetically predicted GERD and PTB.Methods: Initially, we performed bidirectional univariate Mendelian randomization (UVMR) analysis utilizing publicly accessible genome-wide association studies (GWAS) data. The primary analytical approach employed to determine the causal impact between GERD and PTB is the inverse variance weighted technique (IVW). Subsequently, we utilized multivariate Mendelian randomization (MVMR) to adjust for potential factors that could influence the results, such as body mass index (BMI), maternal smoking around birth, educational attainment, household income, and Townsend deprivation index (TDI). Furthermore, we performed a sequence of comprehensive sensitivity analyses to assess the reliability of our MR findings.Results: The UVMR analysis results showed a significant correlation between GERD and PTB (odds ratio [OR]: 1.810; 95% confidence interval [CI]: 1.344– 2.439; P=9.60E-05) in the IVW model, and the Weighted median method (OR=1.591, 95% CI=1.094– 2.315, P=0.015) revealed consistent results. The inverse MR findings suggest no causal link between PTB and the incidence of GERD. In addition, the sensitivity analysis did not detect heterogeneity or horizontal pleiotropy, and the “leave-one-out” examination confirmed that the causal estimation is unlikely to be influenced by the single nucleotide polymorphisms (SNPs) effect. The MVMR analysis demonstrated that the causal association between GERD and PTB still existed after considering BMI, maternal smoking around birth, educational attainment, household income, and TDI (OR=1.921, 95% CI=1.401– 2.634, P=5.08E-05).Conclusion: This study presents evidence indicating that genetically predicted GERD can heighten the risk of PTB. Therefore, it is advisable to perform focused screening for pregnant women with GERD in order to find the initial signs of PTB and promptly apply intervention strategies to extend the duration of pregnancy.Keywords: Mendelian randomization, gastroesophageal reflux disease, preterm birth, causality

Keywords

• mendelian randomization
• gastroesophageal reflux disease
• preterm birth
• causality