Abstract：
BACKGROUND: Gastroesophageal reflux disease (GERD) and chronic rhinosinusitis (CRS) have been shown to be potentially closely related, but the relationship between these conditions, particularly the possibility of a causal link, is not fully understood. This study used Mendelian randomization (MR) to assess the causal relationship between these two disorders.
METHODS: We extracted genome-wide association study data sets for GERD and CRS from publicly available gene summaries, and used MR to conduct a causal inference analysis. The main robustness test used in this study included MR-Egger regression, a leave-one-out sensitivity test, and multivariate MR (MVMR).
RESULTS: GERD increased the risk of developing CRS by 36%, based on the inverse-variance weighted method, a statistically significant association (odds ratio [OR] 1.360, 95% confidence interval [CI] 1.179-1.568, P < 0.001). Other MR assessment methods, such as weighted median, simple mode, and weighted mode, similarly observed a significant increase in the risk of CRS occurrence (OR 1.434, 95% CI 1.186-1.734, P < 0.001; OR 1.927, 95% CI 1.166-3.184, P = 0.013; and OR 1.910, 95% CI 1.222-2.983, P = 0.006, respectively). No significant bias was found in the heterogeneity or pleiotropy tests (P = 0.071 and P = 0.700, respectively). Even after excluding possible mediators using MVMR, GERD appeared to significantly increase the risk of developing CRS (OR 1.013, 95% CI 1.008-1.023, P = 0.002).
CONCLUSIONS: This study provides new, significant evidence that GERD is genetically associated with a higher incidence rate of CRS. However, further research is needed to elucidate the potential underlying biological mechanisms of this relationship.
METHODS: We extracted genome-wide association study data sets for GERD and CRS from publicly available gene summaries, and used MR to conduct a causal inference analysis. The main robustness test used in this study included MR-Egger regression, a leave-one-out sensitivity test, and multivariate MR (MVMR).
RESULTS: GERD increased the risk of developing CRS by 36%, based on the inverse-variance weighted method, a statistically significant association (odds ratio [OR] 1.360, 95% confidence interval [CI] 1.179-1.568, P < 0.001). Other MR assessment methods, such as weighted median, simple mode, and weighted mode, similarly observed a significant increase in the risk of CRS occurrence (OR 1.434, 95% CI 1.186-1.734, P < 0.001; OR 1.927, 95% CI 1.166-3.184, P = 0.013; and OR 1.910, 95% CI 1.222-2.983, P = 0.006, respectively). No significant bias was found in the heterogeneity or pleiotropy tests (P = 0.071 and P = 0.700, respectively). Even after excluding possible mediators using MVMR, GERD appeared to significantly increase the risk of developing CRS (OR 1.013, 95% CI 1.008-1.023, P = 0.002).
CONCLUSIONS: This study provides new, significant evidence that GERD is genetically associated with a higher incidence rate of CRS. However, further research is needed to elucidate the potential underlying biological mechanisms of this relationship.
摘要：
背景：胃食管反流病（GERD）和慢性鼻-鼻窦炎（CRS）可能密切相关，但是这些条件之间的关系，特别是因果关系的可能性，没有完全理解。这项研究使用孟德尔随机化（MR）来评估这两种疾病之间的因果关系。
方法：我们从公开的基因摘要中提取了GERD和CRS的全基因组关联研究数据集，并使用MR进行了因果推断分析。本研究中使用的主要稳健性检验包括MR-Egger回归，留一灵敏度测试，和多变量MR(MVMR)。
结果：GERD使发生CRS的风险增加了36％，基于逆方差加权法，具有统计学意义的相关性（比值比[OR]1.360，95％置信区间[CI]1.179-1.568，P<0.001）。其他MR评估方法，如加权中位数，简单模式，和加权模式，同样观察到CRS发生的风险显著增加(OR1.434,95%CI1.186-1.734,P<0.001;OR1.927,95%CI1.166-3.184,P=0.013;OR1.910,95%CI1.222-2.983,P=0.006).在异质性或多效性测试中没有发现明显的偏差（分别为P=0.071和P=0.700）。即使在使用MVMR排除可能的调解员之后，GERD似乎显着增加发生CRS的风险（OR1.013，95％CI1.008-1.023，P=0.002）。
结论：这项研究提供了新的，有重要证据表明GERD与较高的CRS发病率相关。然而,需要进一步的研究来阐明这种关系潜在的潜在生物学机制.
方法：我们从公开的基因摘要中提取了GERD和CRS的全基因组关联研究数据集，并使用MR进行了因果推断分析。本研究中使用的主要稳健性检验包括MR-Egger回归，留一灵敏度测试，和多变量MR(MVMR)。
结果：GERD使发生CRS的风险增加了36％，基于逆方差加权法，具有统计学意义的相关性（比值比[OR]1.360，95％置信区间[CI]1.179-1.568，P<0.001）。其他MR评估方法，如加权中位数，简单模式，和加权模式，同样观察到CRS发生的风险显著增加(OR1.434,95%CI1.186-1.734,P<0.001;OR1.927,95%CI1.166-3.184,P=0.013;OR1.910,95%CI1.222-2.983,P=0.006).在异质性或多效性测试中没有发现明显的偏差（分别为P=0.071和P=0.700）。即使在使用MVMR排除可能的调解员之后，GERD似乎显着增加发生CRS的风险（OR1.013，95％CI1.008-1.023，P=0.002）。
结论：这项研究提供了新的，有重要证据表明GERD与较高的CRS发病率相关。然而,需要进一步的研究来阐明这种关系潜在的潜在生物学机制.
