The causal effects of lipids and apolipoproteins on idiopathic pulmonary fibrosis: A Mendelian randomization study

Abstract

Abstract Background：There is ambiguous causality observed between lipids and apolipoproteins and the occurrence of idiopathic pulmonary fibrosis (IPF) in some studies, but this has not been confirmed from a genetic perspective. Our aim was to assess the causal effect of lipid and apolipoprotein levels on IPF using the method of Mendelian randomization (MR) analysis. Methods：In our study, we used publicly available genome-wide association summary data (GWAS) to conduct two-sample bidirectional MR and multivariable MR (MVMR) analyses in order to evaluate the relationship between lipid and apolipoprotein levels and IPF. Firstly, we strictly selected eligible SNPs related to exposure based on general screening criteria. Then, MR analysis using inverse variance weighting (IVW) as the main method, we also employed additional methods such as MR-Egger, weighted median, weighted mode, and simple mode to ensure result robustness. We assessed sensitivity through the MR-Egger intercept test, Cochran's Q test, and the "leave-one-out" method. Additionally, we utilized MR-PRESSO as a complementary method to identify horizontal pleiotropy. Results: Our results showed that genetically predicted TG, HDL-C, LDL-C, Apo A-I, and Apo B have no clear causal relationship to IPF based on IVW results, which is inconsistent with many published observational studies. Conclusion: Although many studies have reported a relationship between lipids and apolipoproteins and IPF, our MR results suggest that lipid and apolipoprotein levels may not be causally associated with the risk of IPF.