Causal association of polyunsaturated fatty acids with biliary tract diseases: A Mendelian randomization study

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.

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.

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.

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.