Zheng Qianyou, Wu Ce, Li Yaru, Wu Jing, Tang Wenrui, Zhu Qiuyang, Ren Shaokang, Zhang Xiaowen, Li Shenling, Fu Tao
Department of Otolaryngology, Head and Neck Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
SAGE Open Med. 2025 Apr 21;13:20503121251332151. doi: 10.1177/20503121251332151. eCollection 2025.
While existing research has indicated a potential link between gastroesophageal reflux disease (GERD) and chronic suppurative otitis media (CSOM), these findings primarily stem from observational studies, which are inherently limited by confounding variables and methodological biases, thereby reducing their reliability. This research sought to elucidate the causative link between GERD and CSOM.
A two-sample bidirectional Mendelian randomization (MR) study was conducted using genetic data to assess the causal relationship between GERD and CSOM. Pooled genetic data for GERD and CSOM were obtained from published genomewide association studies. Independent single nucleotide polymorphisms, rigorously screened as instrumental variables, were used in the analysis. The primary analytical method was inverse variance weighting (IVW), with additional sensitivity analyses performed to assess the robustness and reliability of the results.
Per MR analysis, genetically predicted GERD positively associated with an increased CSOM risk (IVW: = 0.001, odds ratio = 2.08, 95% confidence interval: 1.33-3.27). Per reverse MR analysis, genetically predicted CSOM did not associate with an increased GERD risk. Sensitivity analyses did not identify horizontal pleiotropy or heterogeneity.
For the first time, GERD was identified as a risk factor for CSOM through a bidirectional MR study. This finding provides high-level causal evidence for the prevention and management of CSOM and forms a basis for future clinical and mechanistic studies. Clinicians should consider the potential impact of GERD when treating patients with CSOM, as GERD may be an important risk factor.
虽然现有研究表明胃食管反流病(GERD)与慢性化脓性中耳炎(CSOM)之间可能存在联系,但这些发现主要源于观察性研究,这些研究固有地受到混杂变量和方法学偏倚的限制,从而降低了其可靠性。本研究旨在阐明GERD与CSOM之间的因果关系。
采用两样本双向孟德尔随机化(MR)研究,利用遗传数据评估GERD与CSOM之间的因果关系。GERD和CSOM的汇总遗传数据来自已发表的全基因组关联研究。分析中使用了经过严格筛选作为工具变量的独立单核苷酸多态性。主要分析方法为逆方差加权(IVW),并进行了额外的敏感性分析以评估结果的稳健性和可靠性。
根据MR分析,遗传预测的GERD与CSOM风险增加呈正相关(IVW:=0.001,比值比=2.08,95%置信区间:1.33 - 3.27)。根据反向MR分析,遗传预测的CSOM与GERD风险增加无关。敏感性分析未发现水平多效性或异质性。
通过双向MR研究首次将GERD确定为CSOM的一个危险因素。这一发现为CSOM的预防和管理提供了高级别的因果证据,并为未来的临床和机制研究奠定了基础。临床医生在治疗CSOM患者时应考虑GERD的潜在影响,因为GERD可能是一个重要的危险因素。