The causal associations of circulating lipids with Barrett’s Esophagus (BE) and Esophageal Cancer (EC) has been a topic of debate. This study sought to elucidate the causality between circulating lipids and the risk of BE and EC. We conducted two-sample Mendelian randomization (MR) analyses using single nucleotide polymorphisms (SNPs) of circulating lipids (n = 94,595 − 431,167 individuals), BE (218,792 individuals), and EC (190,190 individuals) obtained from the publicly available IEU OpenGWAS database. The robustness and reliability of the results were ensured by employing inverse-variance weighted (IVW), weighted median, MR-Egger, and MR-PRESSO methods. The presence of horizontal pleiotropy, heterogeneities, and stability of instrumental variables were assessed through MR-Egger intercept test, Cochran’s Q test, and leave-one-out sensitivity analysis. Additionally, bidirectional MR and multivariable MR (MVMR) were performed to explore reverse causality and adjust for known confounders, respectively. None of the testing methods revealed statistically significant horizontal pleiotropy, directional pleiotropy, or heterogeneity. Univariate MR analyses using IVW indicated a robust causal relationship between increased triglycerides and BE (odds ratio [OR] = 1.79, p-value = 0.009), while no significant association with EC was observed. Inverse MR analysis indicated no evidence of reverse causality in the aforementioned outcomes. In MVMR analyses, elevated triglycerides (TRG) were significantly and positively associated with BE risk (OR = 1.79, p-value = 0.041). This MR study suggested that genetically increased triglycerides were closely related to an elevated risk of BE, potentially serving as a biomarker for the diagnosis of BE in the future.

中文翻译：

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循环脂质与巴雷特食管和食管癌的因果关系：双向、两个样本孟德尔随机化分析

循环脂质与巴雷特食管（BE）和食管癌（EC）的因果关系一直是争论的话题。本研究旨在阐明循环脂质与 BE 和 EC 风险之间的因果关系。我们使用从公开的 IEU OpenGWAS 数据库获得的循环脂质（n = 94,595 – 431,167 人）、BE（218,792 人）和 EC（190,190 人）的单核苷酸多态性 (SNP) 进行了两个样本孟德尔随机化 (MR) 分析。 。通过采用逆方差加权（IVW）、加权中位数、MR-Egger 和 MR-PRESSO 方法确保了结果的稳健性和可靠性。通过 MR-Egger 截距检验、Cochran's Q 检验和留一敏感性分析来评估工具变量的水平多效性、异质性和稳定性。此外，还进行了双向 MR 和多变量 MR (MVMR)，分别探索反向因果关系并调整已知的混杂因素。没有一种测试方法显示出具有统计显着性的水平多效性、定向多效性或异质性。使用 IVW 的单变量 MR 分析表明甘油三酯增加与 BE 之间存在强有力的因果关系（比值比 [OR] = 1.79，p 值 = 0.009），而与 EC 没有观察到显着关联。反向 MR 分析表明，上述结果中没有反向因果关系的证据。在 MVMR 分析中，甘油三酯 (TRG) 升高与 BE 风险显着呈正相关（OR = 1.79，p 值 = 0.041）。这项 MR 研究表明，遗传性增加的甘油三酯与 BE 风险升高密切相关，可能作为未来诊断 BE 的生物标志物。