Yi Nan, Huang Jun, Deng Zhejun, Liang Yunxiao
Department of Gastroenterology, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.
Medicine (Baltimore). 2025 Aug 15;104(33):e43913. doi: 10.1097/MD.0000000000043913.
The aim of the study was to investigate the causal relationship between chronic obstructive pulmonary disease (COPD) and Barrett's esophagus (BE) using two-sample Mendelian randomization (MR). We obtained summary-level genome-wide association study data on COPD and BE from the integrative epidemiology unit of the open genome-wide association study project, and selected significant single nucleotide polymorphisms as instrumental variables. Various MR analysis methods were employed to assess the causal effect of COPD on BE and vice versa. The methods selected include inverse variance weighted (IVW) analysis, weighted median analysis, and MR-Egger analysis. The MR resonance imaging revealed a bidirectional causal relationship between COPD and BE. IVW analysis indicated that COPD increased the risk of BE (odds ratio [OR]: 1.24, 95% confidence interval [CI]: 1.12-1.34, P = 3.0 × 10⁻⁵), which was supported using the weighted median method (OR = 1.16, 95% CI: 1.01-1.33, P = .04). These findings were robust in the pleiotropy analysis (MR-Egger intercept = 0.02). Conversely, BE also increases the risk of COPD (IVW OR: 1.080, 95% CI: 1.03-1.13, P = .001), with supporting evidence from the weighted median method (OR = 1.09, 95% CI = 1.03-1.15, P = .005). These findings were robust in the pleiotropy analysis (MR-Egger intercept = 0.001). Our study findings reveal a bidirectional causal link between COPD and BE, highlighting the need for mechanistic research to elucidate the underlying pathways. These insights can improve our knowledge of novel screening and prevention strategies, emphasizing the importance of targeted healthcare measures.
本研究旨在采用两样本孟德尔随机化(MR)方法,探究慢性阻塞性肺疾病(COPD)与巴雷特食管(BE)之间的因果关系。我们从开放全基因组关联研究项目的综合流行病学部门获取了关于COPD和BE的汇总水平全基因组关联研究数据,并选择了显著的单核苷酸多态性作为工具变量。采用多种MR分析方法来评估COPD对BE的因果效应,反之亦然。所选用的方法包括逆方差加权(IVW)分析、加权中位数分析和MR-Egger分析。MR成像显示COPD与BE之间存在双向因果关系。IVW分析表明,COPD增加了BE的发病风险(优势比[OR]:1.24,95%置信区间[CI]:1.12 - 1.34,P = 3.0×10⁻⁵),加权中位数法也支持这一结果(OR = 1.16,95% CI:1.01 - 1.33,P = 0.04)。这些发现在多效性分析中具有稳健性(MR-Egger截距 = 0.02)。相反,BE也增加了COPD的发病风险(IVW OR:1.080,95% CI:1.03 - 1.13,P = 0.001),加权中位数法也提供了支持证据(OR = 1.09,95% CI = 1.03 - 1.15,P = 0.005)。这些发现在多效性分析中具有稳健性(MR-Egger截距 = 0.001)。我们的研究结果揭示了COPD与BE之间的双向因果联系,突出了开展机制研究以阐明潜在途径的必要性。这些见解有助于增进我们对新型筛查和预防策略的认识,强调了针对性医疗措施的重要性。
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