Polyunsaturated fatty acids and intrahepatic cholestasis of pregnancy: a two-sample Mendelian randomization analysis

Abstract Objective We aimed to investigate the potential causal relationship between PUFAs and the risk of ICP using Mendelian randomization (MR) analysis. Methods We conducted a two-sample MR analysis using large-scale European-based genome-wide association studies (GWASs) summary data related to ICP containing 115,006 samples. The exposures,including omega-3 fatty acids levels, ratio of omega-3 fatty acids to total fatty acids, ratio of omega-6 fatty acids to omega-3 fatty acids, ratio of linoleic acid to total fatty acids, come from UK Biobank containing 11,590,399 single-nucleotide polymorphisms (SNPs). MR analysis was performed mainly using the inverse variance-weighted (IVW) methods, and other methods including were conducted to validate the result.We also cnducted sensitivity analysis to identify the potential heterogeneity and pleiotropy. Results We found that the risk of ICP was reduced by 31% for every 1SD increase in omega-3 fatty acids levels(OR=0.69, 95%CI=0.54 to 0.89) and in omega-3 fatty acids to total fatty acids(OR=0.69, 95%CI=0.53 to 0.91). The risk of ICP was increased by 51% for every 1SD increase in ratio of omega-6 fatty acids to omega-3 fatty acids(OR=1.51, 95%CI=1.20 to 1.91) and increased by 138% for every 1SD increase in ratio of linoleic fatty acids to total fatty acids (OR = 2.38, 95%CI=1.55 to 3.66). Conclusions Our study suggests that omega-3 fatty acids are protective against the risk of ICP, while omega-6 fatty acids and linoleic fatty acids are potential risk factors for ICP. Omega-3 fatty acids and omega-6 fatty acids can be used as markers for potential risk stratification of ICP.