Department of Emergency, First Affiliated Hospital of Chongqing Medical University, 12th Floor, Building 5A, 1 Youyi Rd, Yuzhong Qu, Chongqing, 400016, People's Republic of China.
Intensive Care Unit, First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Dig Dis Sci. 2024 Oct;69(10):3824-3834. doi: 10.1007/s10620-024-08625-0. Epub 2024 Sep 4.
Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder. Recent studies indicate that GERD may exert systemic effects, potentially elevating the risk of severe infections, including sepsis. Nevertheless, the causal relationship between GERD and sepsis, as well as sepsis-related 28-day mortality, remains uncertain.
The aim of this study is to investigate the causal relationship between GERD and the risk of sepsis, including 28-day mortality of sepsis.
This study utilized a two-sample Mendelian Randomization (MR) approach to analyze data from publicly available genome-wide association studies (GWAS) databases ( https://gwas.mrcieu.ac.uk/ ). The analysis comprised 129,080 cases and 473,524 controls for GERD; 11,643 patients and 474,841 controls for sepsis; and 1,896 patients and 484,588 controls for 28-day mortality from sepsis. The objective was to evaluate the causal impact of GERD on the risk of sepsis and 28-day sepsis mortality. Genetic variation data pertinent to GERD were obtained from the most recent genome-wide association studies (GWAS). The primary analysis employed the Inverse Variance Weighted (IVW) method. Sensitivity and pleiotropy analyses were performed to validate the robustness of the findings.
MR analysis revealed a notable link between genetically predicted GERD and increased sepsis risk (odds ratio [OR] 1.37, 95% confidence interval [CI] 1.24-1.52; p = 2.79 × 10-9). Moreover, GERD correlated with elevated 28-day mortality of sepsis (OR 1.44, 95% CI 1.11-1.85; p = 5.34 × 10-3). These results remained consistent throughout various sensitivity analyses, indicating their resilience against potential pleiotropy and other biases.
This study indicates that genetic predisposition to GERD may be linked to an elevated risk of sepsis and its associated 28-day mortality. However, the study does not establish a direct causal relationship for GERD itself, nor does it assess the impact of GERD treatment. Further research is needed to explore the underlying mechanisms and potential therapeutic interventions involved.
胃食管反流病（GERD）是一种常见的胃肠道疾病。最近的研究表明，GERD 可能会产生全身影响，潜在增加严重感染的风险，包括败血症。然而，GERD 与败血症之间的因果关系以及败血症相关的 28 天死亡率仍然不确定。
本研究旨在探讨 GERD 与败血症风险之间的因果关系，包括败血症的 28 天死亡率。
本研究采用两样本 Mendelian Randomization（MR）方法，分析来自公开的全基因组关联研究（GWAS）数据库的数据（https://gwas.mrcieu.ac.uk/）。分析包括 129080 例 GERD 病例和 473524 例对照；11643 例败血症患者和 474841 例对照；1896 例败血症 28 天死亡率患者和 484588 例对照。目的是评估 GERD 对败血症风险和败血症 28 天死亡率的因果影响。与 GERD 相关的遗传变异数据来自最近的全基因组关联研究（GWAS）。主要分析采用Inverse Variance Weighted（IVW）方法。进行敏感性和多效性分析以验证结果的稳健性。
MR 分析表明，遗传预测的 GERD 与败血症风险增加之间存在显著关联（比值比[OR]1.37，95%置信区间[CI]1.24-1.52；p=2.79×10-9）。此外，GERD 与败血症 28 天死亡率升高相关（OR 1.44，95% CI 1.11-1.85；p=5.34×10-3）。这些结果在各种敏感性分析中仍然一致，表明它们对潜在的多效性和其他偏差具有抵抗力。
本研究表明，GERD 的遗传易感性可能与败血症风险及其相关的 28 天死亡率升高有关。然而，该研究并未确定 GERD 本身的直接因果关系，也未评估 GERD 治疗的影响。需要进一步研究来探索潜在的机制和潜在的治疗干预措施。
