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. 2023 Apr 5:14:1111144.
doi: 10.3389/fgene.2023.1111144. eCollection 2023.

Causal association between obstructive sleep apnea and gastroesophageal reflux disease: A bidirectional two-sample Mendelian randomization study

Qianyin Zhu  1 , Lijiangshan Hua  1 , Lingshan Chen  1 , Tingyu Mu  1 , Die Dong  1 , Jiayi Xu  1 , Cuizhen Shen  1
Affiliations

Causal association between obstructive sleep apnea and gastroesophageal reflux disease: A bidirectional two-sample Mendelian randomization study

Qianyin Zhu et al. Front Genet. .

Abstract

Objectives: Correlations between obstructive sleep apnea (OSA) and gastroesophageal reflux disease (GERD) have been detected in previous observational studies. However, this association remains uncertain due to the potential presence of selection and confounding biases. Therefore, this bidirectional two-sample Mendelian randomization (MR) study was conducted to evaluate the causal relationship between OSA and GERD. Methods: In this study, instrumental variables (IVs) for OSA were selected from publicly available genetic summary data (27,207 cases and 280,720 controls). Summary statistics for GERD were obtained from a genome-wide association study of 602,604 individuals. The inverse variance weighted (IVW) method was used as the main MR method. The MR-Egger intercept test, MR pleiotropy residual sum and outlier, and leave-one-out analysis were used to detect pleiotropy. Heterogeneity was detected by Cochran's Q test. Results: The IVW results revealed that OSA [odds ratio (OR): 1.19, 95% confidence interval (CI): 1.11-1.28, p = 8.88E-07] was causally associated with the incidence of GERD. Moreover, there was evidence of GERD leading to OSA in the IVW analysis (OR: 1.44, 95%CI: 1.33-1.57, p = 7.74E-19). No directional pleiotropy was detected by the MR-Egger intercept test (all p > 0.05). Conclusion: This study found that OSA is linked to a higher incidence of GERD, and vice versa. This finding might be helpful for the screening and prevention of these two diseases.

Keywords: Mendelian randomization; bidirectional; causal; gastroesophageal reflux disease; obstructive sleep apnea.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Workflow of the bidirectional two-sample MR study. Abbreviation: MR, Mendelian randomization; OSA, obstructive sleep apnea; GERD, gastroesophageal reflux disease; SNP, single nucleotide polymorphism; PRESSO, Pleiotropy REsidual Sum and Outlier; IVW, inverse variance weighted.
FIGURE 2
FIGURE 2
Two-sample MR estimates results of causal associations between OSA and GERD. (A) Causal estimates result for OSA on GERD. (B) Causal estimates result for GERD on OSA. Abbreviation: MR, Mendelian randomization; OSA, obstructive sleep apnea; GERD, gastroesophageal reflux disease; IVW, inverse variance weighted; N. SNPs is the number of SNPs after outliers removed; SNPs, single nucleotide polymorphisms; OR, odds ratio; CI, confidence interval.
FIGURE 3
FIGURE 3
Scatter plot for the causal relationship of OSA on GERD. MR, Mendelian randomization; SNP, single nucleotide polymorphism; OSA, obstructive sleep apnea; GERD, gastroesophageal reflux disease.
FIGURE 4
FIGURE 4
Forest plot for the causal relationship of OSA on GERD. MR, Mendelian randomization; OSA, obstructive sleep apnea; GERD, gastroesophageal reflux disease.
FIGURE 5
FIGURE 5
Scatter plot for the causal relationship of GERD on OSA. Abbreviation: MR, Mendelian randomization; SNP, single nucleotide polymorphism; GERD, gastroesophageal reflux disease; OSA, obstructive sleep apnea.
FIGURE 6
FIGURE 6
Forest plot for the causal relationship of GERD on OSA. Abbreviation: MR, Mendelian randomization; GERD, gastroesophageal reflux disease; OSA, obstructive sleep apnea.
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