Abstract
Our objective is to evaluate the causal interconnection between plasma lipidome (PL) and liver cirrhosis (LC) and to delineate the function of immune cells (ICs) as potential mediators. Extensive genome-wide association study summary data were utilized to analyze the PL, ICs, and LC, and the connection between them was investigated by Mendelian randomization. This study identified 7 significantly causal links, indicating that genetically determined levels of sterol ester phosphatidylcholine (PC) species, particularly PC (15:0_18:2, 16:0_18:2, 18:0_18:1, O-18:1_16:0, O-18:1_18:2, respectively), and phosphatidylethanolamine (O-16:1_18:2) were significantly correlated with a reduced risk of developing LC. In contrast, genetically predicted levels of triglyceride (48:2) are significantly associated with elevated risk of LC. Our study identified 24 ICs associated with LC, including 14 ICs that were positively correlated and 10 ICs that were negatively correlated. Furthermore, we identified several ICs that mediate the effects of the PL on LC. Our findings indicate that PC (18:0_18:1) levels exert their effect on LC through CD127 expression on CD28+ CD45RA+ CD8bright cells, while triglyceride (48:2) levels influence LC via Basophil% CD33dim HLA DR- CD66b- cells as well as HLA DR on CD33dim HLA DR+ CD11b- cells. Our study provides innovative perspectives into the critical roles of PL and ICs in LC development, highlighting their potential as targets for future research and treatment.