Mendelian randomization study of gastroesophageal reflux disease and major depression

Xiaofei Zheng; Xin Zhou; Li Tong; Wang Gu; Siyu Wang; Wenkang Yuang; Chong Zhang; Chaoyang Zhang; Chao Zhang; Bangbei Wan

doi:10.1371/journal.pone.0291086

Mendelian randomization study of gastroesophageal reflux disease and major depression

PLoS One. 2023 Sep 28;18(9):e0291086. doi: 10.1371/journal.pone.0291086. eCollection 2023.

Authors

Xiaofei Zheng¹, Xin Zhou², Li Tong¹, Wang Gu¹, Siyu Wang³, Wenkang Yuang³, Chong Zhang³, Chaoyang Zhang⁴, Chao Zhang¹, Bangbei Wan³

Affiliations

¹ Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
² Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, China.
³ Reproductive Medical Center, Hainan Women and Children's Medical Center, Haikou, China.
⁴ Department of General Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Abstract

This study systematically investigated the causal relationship between gastroesophageal reflux disease (GERD) and major depression (MD). Single-nucleotide polymorphisms (SNPs) associated with disorders of interest were screened via the genome-wide association study (GWAS) enrolling individuals of European descent. Summary-level data for GERD and MD were extracted from the UK Biobank. The inverse-variance-weighted (IVW) method was utilized as the primary analysis. Sensitivity analyses were performed using the MR-Egger method, the Maximum likelihood method, the MR-pleiotropy residual sum outlier (MR-PRESSO) method, and MR-robust adjusted profile score (MR-RAPS) method. MR-Egger regression, heterogeneity tests, pleiotropy tests, and leave-one-out tests were also performed to analyze sensitivity. The MR Steiger test was used to verify the directionality of the exposure to the outcome. An available website tool (https://shiny.cnsgenomics.com/mRnd/) was used to calculate the statistical power of MR analysis. Meta-analysis was applied to test MD's average genetically predicted effect on GERD. Our MR study showed a bidirectional causal association between MD and GERD. Regarding MD to GERD, there was a positive association between them; the ORs were 1.500 (95% CI = 1.320-1.704; P = 4.91E-10) and 2.058 (95% CI = 1.868-2.267; P = 2.20E-48) in the IVW method, respectively. In addition, the meta-analysis also showed a strong positive causal association between MD and GERD. When exposure and outcome were reversed, genetic predisposition to GERD was significantly associated with the overall Risk of advanced MD (ieu-a-1187, OR = 1.982, 95% CI = 1.694-2.319, P = 1.41E-17; ieu-b-102, OR = 1.612, 95% CI = 1.530-2.700, P = 1.15E-70). Our study provides 100% power to detect the causal effect of MD on GERD and vice versa. Genetically predicted MD was positively associated with higher GERD risk, and vice versa. Our study reminds clinicians to pay attention to screening for GERD when diagnosing and treating MD and vice versa. Moreover, there may be positive feedback between MD and GERD when treating and preventing one disorder may benefit the treatment and prevention of the other.

Copyright: © 2023 Zheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Grants and funding

This work was supported by the Hainan Province Clinical Medical Center (No. QWYH202175), the Scientific Research Project of Hainan Health Committee (No. 21A200115), the Research and Cultivation Fund of Hainan Medical University (No. HYPY2020015), the specific research fund of The Innovation Platform for Academicians of Hainan Province, the Natural Science Foundation of Hainan Province (No. 820RC771), and the Key R&D Projects of Hainan Province (No. ZDYF2022SHFZ074, No. ZDYF2022SHFZ280, No. ZDYF2017086, and No. ZDYF2019157). The funders had no role in study design, data collection, and analysis, the decision to publish, or the preparation of the manuscript.