Department of Thoracic Surgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei Province, People's Republic of China.
Department of Ophthalmology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei Province, People's Republic of China.
BMC Med Genomics. 2024 Aug 9;17(1):204. doi: 10.1186/s12920-024-01986-5.
Previous studies have shown that physical activity (PA) and leisure sedentary behaviors (LSB, including leisure television watching) are linked to gastroesophageal reflux disease (GERD). However, the associations between PA/LSB and GERD remain controversial. In this study, we aimed to reveal whether these associations reflect causal relationships and reveal the potential mechanisms of these relationships using bidirectional and two-step Mendelian randomization (MR) analyses.
We obtained genome-wide association study (GWAS) summary statistics for PA/LSB, four common risk factors (including cigarettes smoked per day, alcoholic drinks per week, triglycerides, total cholesterol) and GERD from published GWASs. A bidirectional MR analysis was performed to identify causal relationships between PA/LSB and GERD. Then, a series of sensitivity analyses were performed to verify the robustness of the results. Finally, a mediation analysis via two-step MR was conducted to investigate any effects explained by common risk factors in these relationships.
Genetically predicted per 1-SD increase in leisure time television watching significantly increased the risk of GERD in the bidirectional MR analysis (OR = 1.33; 95% CI: 1.14-1.56; P = 2.71 × 10). Sensitivity analyses successfully verified the robustness of the causal relationship. Further mediation analysis showed that this effect was partly mediated by increasing cigarettes smoked per day, with mediated proportions of 18.37% (95% CI: 11.94-39.79%).
Our findings revealed a causal relationship between leisure television watching and an increased risk of GERD, notably, the causal effect was partially mediated by cigarettes smoked per day. These findings may inform prevention and management strategies directed toward GERD.
先前的研究表明，身体活动（PA）和休闲久坐行为（LSB，包括休闲看电视）与胃食管反流病（GERD）有关。然而，PA/LSB 与 GERD 之间的关联仍存在争议。在这项研究中，我们旨在使用双向和两步孟德尔随机化（MR）分析来揭示这些关联是否反映因果关系，并揭示这些关系的潜在机制。
我们从已发表的 GWAS 中获得了关于 PA/LSB、四个常见风险因素（包括每天吸烟量、每周饮酒量、甘油三酯、总胆固醇）和 GERD 的全基因组关联研究（GWAS）汇总统计数据。进行了双向 MR 分析以确定 PA/LSB 和 GERD 之间的因果关系。然后，进行了一系列敏感性分析以验证结果的稳健性。最后，通过两步 MR 进行中介分析，以调查这些关系中常见风险因素所解释的任何影响。
在双向 MR 分析中，遗传预测的休闲时间看电视每增加 1-SD，GERD 的风险显著增加（OR=1.33；95%CI：1.14-1.56；P=2.71×10）。敏感性分析成功验证了因果关系的稳健性。进一步的中介分析表明，这种影响部分是通过增加每天吸烟量来介导的，介导比例为 18.37%（95%CI：11.94-39.79%）。
我们的研究结果揭示了休闲看电视与 GERD 风险增加之间存在因果关系，特别是，因果效应部分是通过每天吸烟量来介导的。这些发现可能为 GERD 的预防和管理策略提供信息。
