Unraveling the Genetic Links Between Plasma Lipidome and Ankylosing Spondylitis: Insights from a Two-Sample Mendelian Randomization Approach

Abstract

Background: Emerging epidemiological evidence indicates an association between Plasma Lipidome and Ankylosing Spondylitis (AS), yet our grasp of the underlying genetic and causative links remains nascent. This study endeavors to unravel the genetic interplay and assess the causality within this association. Methods: This investigation utilized a two-sample Mendelian Randomization (MR) technique to discern the causal dynamics between lipid profiles and AS. To ascertain causal relationships among 179 distinct lipid molecules and AS susceptibility, we capitalized on extensive GWAS data. The primary analytical tool was the inverse variance weighted (IVW) method, complemented by MR Egger, weighted median, Weighted mode, and Simple mode analyses to ensure comprehensiveness. To assess result consistency, the Cochrane Q-test gauged heterogeneity and the MR-Egger intercept test, alongside MR-PRESSO, scrutinized for horizontal pleiotropy. Lastly, a leave-one-out sensitivity analysis authenticated the findings' stability. Results: The results indicated that levels of Sterol ester (27:1/18:0), Sterol ester (27:1/18:2), Phosphatidylethanolamine (18:1_0:0), Phosphatidylcholine (16:1_18:1), Phosphatidylcholine (16:1_20:4), Phosphatidylcholine (17:0_18:2), Phosphatidylcholine (18:0_20:3), Phosphatidylcholine (18:0_22:6), Phosphatidylcholine (O-16:0_20:4), Phosphatidylcholine (O-18:1_18:2), Phosphatidylinositol (18:1_18:2), Triacylglycerol (50:3), Triacylglycerol (54:3), and Triacylglycerol (56:8) were genetically predicted as consequences of AS. There was no evidence of horizontal pleiotropy or heterogeneity between the genetic variants (P>0.05), and a leave-one-out test confirmed the stability and robustness of this association. Conclusion: Our study deepens the understanding of the genetic research into the close connection between lipid levels and AS, providing guidance for future clinical and basic research.