Abstract：
OBJECTIVE: The evidence connecting polyunsaturated fatty acids (PUFAs) to biliary problems is still highly contested and speculative despite the fact that biliary diseases are common and PUFAs have long been studied for their potential health benefits. This work used Mendelian randomization (MR) techniques in conjunction with genome-wide association study (GWAS) data to clarify the causal relationships between PUFAs and biliary tract diseases.
METHODS: We compiled data on PUFAs, including Omega-3 fatty acids, Omega-6 fatty acids, and the ratio of Omega-6 to Omega-3 fatty acids (Omega-6:Omega-3), using GWAS. MR was used to examine biliary tract problems (cholecystitis, cholelithiasis, gallbladder cancer, primary biliary cholangitis, primary sclerosing cholangitis, and disorders of gallbladder, biliary tract and pancreas). Single nucleotide polymorphisms significantly associated with PUFAs were selected as instrumental variables to estimate causal effects on biliary tract diseases. The final results were analyzed using five MR analysis techniques. Inverse variance weighting (IVW) was used as the primary outcome. And IVW was utilized in conjunction with the other MR analysis techniques (MR-Egger, weighted median, simple mode, and weighted mode). Additionally, we evaluated heterogeneity and horizontal multiplicity using the MR-Egger intercept test and Cochrane\'s Q test, respectively. Finally, to increase the accuracy and precision of the study outcomes, we carried out a number of sensitivity analyses.
RESULTS: We found that Omega-3 fatty acids reduced the risk of cholecystitis (OR: 0.851, P = 0.009), cholelithiasis (OR: 0.787, P = 8.76e-5), and disorders of gallbladder, biliary tract and pancreas (OR: 0.842, P = 1.828e-4) but increased the primary biliary cholangitis (OR: 2.220, P = 0.004). There was no significant association between Omega-3 fatty acids and risk of gallbladder cancer (OR: 3.127, P = 0.530) and primary sclerosing cholangitis (OR: 0.919, P = 0.294). Omega-6 fatty acids were associated with a reduced risk of cholecystitis (OR: 0.845, P = 0.040). However, they were not linked to an increased or decreased risk of cholelithiasis (OR: 0.878, P = 0.14), gallbladder cancer (OR: 4.670, P = 0.515), primary sclerosing cholangitis (OR: 0.993, P = 0.962), primary cholestatic biliary cholangitis (OR: 1.404, P = 0.509), or disorders of gallbladder, biliary tract and pancreas. Omega-6:Omega-3 fatty acids were linked to a greater risk of cholecystitis, cholelithiasis, and disorders of gallbladder, biliary tract and pancreas (OR:1.168, P = 0.009, OR:1.191, P = 1.60e-6, and OR:1.160, P = 4.11e-6, respectively). But (OR: 0.315, P = 0.010) was linked to a decreased risk of primary biliary cholangitis. Not linked to risk of primary sclerosing cholangitis (OR: 1.079, P = 0.078) or gallbladder cancer (OR: 0.046, P = 0.402). According to the MR-Egger intercept, our MR examination did not appear to be impacted by any pleiotropy (all P > 0.05). Additionally, sensitivity studies validated the accuracy of the calculated causation.
CONCLUSIONS: Inconsistent causative relationships between PUFAs and biliary tract diseases were revealed in our investigation. However, Omega-3 fatty acids were found to causally lower the risk of cholecystitis, cholelithiasis, and disorders of gallbladder, biliary tract and pancreas. Omega-3 fatty acids increased the risk of primary biliary cholangitis in a causative way. Omega-3 fatty acids with the risk of gallbladder cancer and primary sclerosing cholangitis did not have any statistically significant relationships. Omega-6 fatty acids were not significantly causally connected with the risk of cholelithiasis, gallbladder cancer, primary sclerosing cholangitis, or disorders of gallbladder, biliary tract and pancreas. However, they did play a causative role in lowering the risk of cholecystitis. Omega-6:Omega-3 fatty acids decreased the risk of primary biliary cholangitis but increased the risk of cholecystitis, gallstone disease, and disorders of gallbladder, biliary tract and pancreas. They had no effect on the risk of gallbladder cancer or primary sclerosing cholangitis. Therefore, additional research should be done to examine the probable processes mediating the link between polyunsaturated fatty acids and the risk of biliary tract diseases.
METHODS: We compiled data on PUFAs, including Omega-3 fatty acids, Omega-6 fatty acids, and the ratio of Omega-6 to Omega-3 fatty acids (Omega-6:Omega-3), using GWAS. MR was used to examine biliary tract problems (cholecystitis, cholelithiasis, gallbladder cancer, primary biliary cholangitis, primary sclerosing cholangitis, and disorders of gallbladder, biliary tract and pancreas). Single nucleotide polymorphisms significantly associated with PUFAs were selected as instrumental variables to estimate causal effects on biliary tract diseases. The final results were analyzed using five MR analysis techniques. Inverse variance weighting (IVW) was used as the primary outcome. And IVW was utilized in conjunction with the other MR analysis techniques (MR-Egger, weighted median, simple mode, and weighted mode). Additionally, we evaluated heterogeneity and horizontal multiplicity using the MR-Egger intercept test and Cochrane\'s Q test, respectively. Finally, to increase the accuracy and precision of the study outcomes, we carried out a number of sensitivity analyses.
RESULTS: We found that Omega-3 fatty acids reduced the risk of cholecystitis (OR: 0.851, P = 0.009), cholelithiasis (OR: 0.787, P = 8.76e-5), and disorders of gallbladder, biliary tract and pancreas (OR: 0.842, P = 1.828e-4) but increased the primary biliary cholangitis (OR: 2.220, P = 0.004). There was no significant association between Omega-3 fatty acids and risk of gallbladder cancer (OR: 3.127, P = 0.530) and primary sclerosing cholangitis (OR: 0.919, P = 0.294). Omega-6 fatty acids were associated with a reduced risk of cholecystitis (OR: 0.845, P = 0.040). However, they were not linked to an increased or decreased risk of cholelithiasis (OR: 0.878, P = 0.14), gallbladder cancer (OR: 4.670, P = 0.515), primary sclerosing cholangitis (OR: 0.993, P = 0.962), primary cholestatic biliary cholangitis (OR: 1.404, P = 0.509), or disorders of gallbladder, biliary tract and pancreas. Omega-6:Omega-3 fatty acids were linked to a greater risk of cholecystitis, cholelithiasis, and disorders of gallbladder, biliary tract and pancreas (OR:1.168, P = 0.009, OR:1.191, P = 1.60e-6, and OR:1.160, P = 4.11e-6, respectively). But (OR: 0.315, P = 0.010) was linked to a decreased risk of primary biliary cholangitis. Not linked to risk of primary sclerosing cholangitis (OR: 1.079, P = 0.078) or gallbladder cancer (OR: 0.046, P = 0.402). According to the MR-Egger intercept, our MR examination did not appear to be impacted by any pleiotropy (all P > 0.05). Additionally, sensitivity studies validated the accuracy of the calculated causation.
CONCLUSIONS: Inconsistent causative relationships between PUFAs and biliary tract diseases were revealed in our investigation. However, Omega-3 fatty acids were found to causally lower the risk of cholecystitis, cholelithiasis, and disorders of gallbladder, biliary tract and pancreas. Omega-3 fatty acids increased the risk of primary biliary cholangitis in a causative way. Omega-3 fatty acids with the risk of gallbladder cancer and primary sclerosing cholangitis did not have any statistically significant relationships. Omega-6 fatty acids were not significantly causally connected with the risk of cholelithiasis, gallbladder cancer, primary sclerosing cholangitis, or disorders of gallbladder, biliary tract and pancreas. However, they did play a causative role in lowering the risk of cholecystitis. Omega-6:Omega-3 fatty acids decreased the risk of primary biliary cholangitis but increased the risk of cholecystitis, gallstone disease, and disorders of gallbladder, biliary tract and pancreas. They had no effect on the risk of gallbladder cancer or primary sclerosing cholangitis. Therefore, additional research should be done to examine the probable processes mediating the link between polyunsaturated fatty acids and the risk of biliary tract diseases.
摘要：
目的：尽管胆道疾病很常见，但将多不饱和脂肪酸（PUFA）与胆道疾病联系起来的证据仍然存在争议和推测性，并且长期以来一直对PUFA的潜在健康益处进行研究。这项工作使用孟德尔随机化（MR）技术与全基因组关联研究（GWAS）数据相结合，以阐明PUFA与胆道疾病之间的因果关系。
方法：我们在PUFA上编译了数据，包括Omega-3脂肪酸,Omega-6脂肪酸,以及Omega-6与Omega-3脂肪酸的比例（Omega-6：Omega-3），使用GWAS。MR用于检查胆道问题（胆囊炎，胆石症,胆囊癌,原发性胆汁性胆管炎,原发性硬化性胆管炎,和胆囊疾病，胆道和胰腺）。选择与PUFA显着相关的单核苷酸多态性作为工具变量，以估计对胆道疾病的因果关系。使用五种MR分析技术分析最终结果。使用反向方差加权(IVW)作为主要结果。IVW与其他MR分析技术(MR-Egger，加权中位数，简单模式，和加权模式)。此外,我们使用MR-Egger截距检验和Cochrane的Q检验评估了异质性和水平多重性，分别。最后,为了提高研究结果的准确性和精确度，我们进行了一些敏感性分析.
结果：我们发现Omega-3脂肪酸可降低胆囊炎的风险（OR：0.851，P=0.009），胆石症（OR：0.787，P=8.76e-5），和胆囊疾病，胆道和胰腺（OR：0.842，P=1.828e-4），但增加原发性胆汁性胆管炎（OR：2.220，P=0.004）。Omega-3脂肪酸与胆囊癌（OR：3.127，P=0.530）和原发性硬化性胆管炎（OR：0.919，P=0.294）的风险之间没有显着关联。Omega-6脂肪酸与胆囊炎风险降低相关(OR:0.845,P=0.040)。然而,它们与胆石症的风险增加或降低无关（OR：0.878，P=0.14），胆囊癌（OR：4.670，P=0.515），原发性硬化性胆管炎（OR：0.993，P=0.962），原发性胆汁淤积性胆管炎(OR:1.404,P=0.509),或者胆囊疾病，胆道和胰腺。Omega-6：Omega-3脂肪酸与胆囊炎的风险更大，胆石症,和胆囊疾病，胆道和胰腺（OR：1.168，P=0.009，OR：1.191，P=1.60e-6和OR：1.160，P=4.11e-6）。但是（OR：0.315，P=0.010）与原发性胆汁性胆管炎的风险降低有关。与原发性硬化性胆管炎（OR：1.079，P=0.078）或胆囊癌（OR：0.046，P=0.402）的风险无关。根据MR-Egger截获,我们的MR检查似乎未受到任何多效性的影响(均P>0.05).此外,敏感性研究验证了计算因果关系的准确性。
结论：在我们的调查中揭示了PUFA与胆道疾病之间不一致的因果关系。然而,Omega-3脂肪酸被发现降低胆囊炎的风险，胆石症,和胆囊疾病，胆道和胰腺。Omega-3脂肪酸以致病方式增加了原发性胆汁性胆管炎的风险。Omega-3脂肪酸与胆囊癌和原发性硬化性胆管炎的风险没有任何统计学上的显着关系。Omega-6脂肪酸与胆石症的风险没有显着因果关系，胆囊癌,原发性硬化性胆管炎,或者胆囊疾病，胆道和胰腺。然而,它们确实在降低胆囊炎风险方面发挥了致病作用。Omega-6：Omega-3脂肪酸降低原发性胆汁性胆管炎的风险，但增加胆囊炎的风险，胆结石病,和胆囊疾病，胆道和胰腺。他们对胆囊癌或原发性硬化性胆管炎的风险没有影响。因此,应该做更多的研究来检查多不饱和脂肪酸与胆道疾病风险之间可能的中介过程。
方法：我们在PUFA上编译了数据，包括Omega-3脂肪酸,Omega-6脂肪酸,以及Omega-6与Omega-3脂肪酸的比例（Omega-6：Omega-3），使用GWAS。MR用于检查胆道问题（胆囊炎，胆石症,胆囊癌,原发性胆汁性胆管炎,原发性硬化性胆管炎,和胆囊疾病，胆道和胰腺）。选择与PUFA显着相关的单核苷酸多态性作为工具变量，以估计对胆道疾病的因果关系。使用五种MR分析技术分析最终结果。使用反向方差加权(IVW)作为主要结果。IVW与其他MR分析技术(MR-Egger，加权中位数，简单模式，和加权模式)。此外,我们使用MR-Egger截距检验和Cochrane的Q检验评估了异质性和水平多重性，分别。最后,为了提高研究结果的准确性和精确度，我们进行了一些敏感性分析.
结果：我们发现Omega-3脂肪酸可降低胆囊炎的风险（OR：0.851，P=0.009），胆石症（OR：0.787，P=8.76e-5），和胆囊疾病，胆道和胰腺（OR：0.842，P=1.828e-4），但增加原发性胆汁性胆管炎（OR：2.220，P=0.004）。Omega-3脂肪酸与胆囊癌（OR：3.127，P=0.530）和原发性硬化性胆管炎（OR：0.919，P=0.294）的风险之间没有显着关联。Omega-6脂肪酸与胆囊炎风险降低相关(OR:0.845,P=0.040)。然而,它们与胆石症的风险增加或降低无关（OR：0.878，P=0.14），胆囊癌（OR：4.670，P=0.515），原发性硬化性胆管炎（OR：0.993，P=0.962），原发性胆汁淤积性胆管炎(OR:1.404,P=0.509),或者胆囊疾病，胆道和胰腺。Omega-6：Omega-3脂肪酸与胆囊炎的风险更大，胆石症,和胆囊疾病，胆道和胰腺（OR：1.168，P=0.009，OR：1.191，P=1.60e-6和OR：1.160，P=4.11e-6）。但是（OR：0.315，P=0.010）与原发性胆汁性胆管炎的风险降低有关。与原发性硬化性胆管炎（OR：1.079，P=0.078）或胆囊癌（OR：0.046，P=0.402）的风险无关。根据MR-Egger截获,我们的MR检查似乎未受到任何多效性的影响(均P>0.05).此外,敏感性研究验证了计算因果关系的准确性。
结论：在我们的调查中揭示了PUFA与胆道疾病之间不一致的因果关系。然而,Omega-3脂肪酸被发现降低胆囊炎的风险，胆石症,和胆囊疾病，胆道和胰腺。Omega-3脂肪酸以致病方式增加了原发性胆汁性胆管炎的风险。Omega-3脂肪酸与胆囊癌和原发性硬化性胆管炎的风险没有任何统计学上的显着关系。Omega-6脂肪酸与胆石症的风险没有显着因果关系，胆囊癌,原发性硬化性胆管炎,或者胆囊疾病，胆道和胰腺。然而,它们确实在降低胆囊炎风险方面发挥了致病作用。Omega-6：Omega-3脂肪酸降低原发性胆汁性胆管炎的风险，但增加胆囊炎的风险，胆结石病,和胆囊疾病，胆道和胰腺。他们对胆囊癌或原发性硬化性胆管炎的风险没有影响。因此,应该做更多的研究来检查多不饱和脂肪酸与胆道疾病风险之间可能的中介过程。
