PDF(Pubmed)
Abstract：
Rheumatoid arthritis (RA) is a common autoimmune disease, and some observational studies have indicated an association between Gastroesophageal Reflux Disease (GERD) and RA. However, the causal relationship between the two remains uncertain. We used Mendelian randomization (MR) to assess the causal relationship between GERD and RA. Two-sample Mendelian randomization analysis was performed using pooled data from large-scale genome-wide association studies. In addition, we performed multivariate MR analyses to exclude confounding factors between GERD and RA, including smoking quantity, drinking frequency, BMI, depression, and education attainment. The MR results for GERD on RA suggested a causal effect of the genetic susceptibility of GERD on RA (discovery dataset, IVW, odds ratio [OR] = 1.41, 95% confidence interval [CI] 1.22-1.63, p = 2.81 × 10-6; validation dataset, IVW, OR = 1.38, 95% CI 1.23-1.55, P = 1.76 × 10-8). Multivariate MR analysis also supports this result. But the results of the reverse MR analysis did not reveal compelling evidence that RA can increase the risk of developing GERD. Our bidirectional Two-Sample Mendelian randomization analysis and multivariate MR analysis provide support for the causal effect of GERD on RA. This discovery could offer new insights for the prevention and treatment of RA.
摘要：
类风湿性关节炎(RA)是一种常见的自身免疫性疾病,一些观察性研究表明胃食管反流病（GERD）与RA之间存在关联。然而,两者之间的因果关系仍然不确定。我们使用孟德尔随机化（MR）来评估GERD和RA之间的因果关系。使用来自大规模全基因组关联研究的合并数据进行两个样本孟德尔随机化分析。此外,我们进行了多变量MR分析，以排除GERD和RA之间的混杂因素，包括吸烟量，饮酒频率,BMI,抑郁症,和教育程度。GERD对RA的MR结果表明GERD对RA的遗传易感性有因果关系（发现数据集，IVW,优势比[OR]=1.41，95%置信区间[CI]1.22-1.63，p=2.81×10-6；验证数据集，IVW,OR=1.38，95%CI1.23-1.55，P=1.76×10-8）。多变量MR分析也支持该结果。但是反向MR分析的结果并没有揭示有说服力的证据表明RA可以增加发展为GERD的风险。我们的双向双样本孟德尔随机化分析和多变量MR分析为GERD对RA的因果效应提供了支持。这一发现可以为RA的预防和治疗提供新的见解。
