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Abstract：
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
摘要：
目的：循环脂质与Barrett食管（BE）和食管癌（EC）的因果关系一直是争论的话题。这项研究试图阐明循环脂质与BE和EC风险之间的因果关系。
方法：我们使用循环脂质的单核苷酸多态性（SNP）进行了两个样本孟德尔随机化（MR）分析（n=94,595-431,167个人），BE（218,792人），和EC（190,190人）从公开的IEUOpenGWAS数据库获得。采用逆方差加权(IVW)，保证了结果的稳健性和可靠性。加权中位数，MR-Egger,和MR-PRESSO方法。水平多效性的存在，异质性，通过MR-Egger截距检验评估工具变量的稳定性，Cochran的Q测试,和留一法敏感性分析。此外,双向MR和多变量MR(MVMR)进行了探索反向因果关系和调整已知的混杂因素，分别。
结果：所有测试方法均未显示具有统计学意义的水平多效性，方向性多效性，或异质性。使用IVW的单变量MR分析表明，甘油三酯增加与BE之间存在可靠的因果关系（比值比[OR]=1.79，p值=0.009），而未观察到与EC的显著关联。反向MR分析表明在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风险显著正相关(OR=1.79,p值=0.041).
结论：这项MR研究表明，遗传上增加的甘油三酯与BE风险升高密切相关，有可能作为未来诊断BE的生物标志物。
方法：我们使用循环脂质的单核苷酸多态性（SNP）进行了两个样本孟德尔随机化（MR）分析（n=94,595-431,167个人），BE（218,792人），和EC（190,190人）从公开的IEUOpenGWAS数据库获得。采用逆方差加权(IVW)，保证了结果的稳健性和可靠性。加权中位数，MR-Egger,和MR-PRESSO方法。水平多效性的存在，异质性，通过MR-Egger截距检验评估工具变量的稳定性，Cochran的Q测试,和留一法敏感性分析。此外,双向MR和多变量MR(MVMR)进行了探索反向因果关系和调整已知的混杂因素，分别。
结果：所有测试方法均未显示具有统计学意义的水平多效性，方向性多效性，或异质性。使用IVW的单变量MR分析表明，甘油三酯增加与BE之间存在可靠的因果关系（比值比[OR]=1.79，p值=0.009），而未观察到与EC的显著关联。反向MR分析表明在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风险显著正相关(OR=1.79,p值=0.041).
结论：这项MR研究表明，遗传上增加的甘油三酯与BE风险升高密切相关，有可能作为未来诊断BE的生物标志物。
