<p>This study investigates the potential causal relationships among immune cells, plasma liposomes, and plasma metabolites in allergic rhinitis (AR) using a two-sample bidirectional multivariate and mediated Mendelian Randomization (MR) approach. Genetic data from five GWAS datasets covering traits linked to immune cells, plasma liposomes, plasma metabolites, and AR were used. Instrumental variables were selected based on strict criteria to ensure independence and exclude confounders. The primary MR analysis employed the Inverse Variance Weighted method, supplemented by sensitivity analyses using the Weighted Median and MR-Egger methods. The MR analyses suggest a genetic correlation among immune cells, plasma liposomes, and plasma metabolites, influencing the risk of AR. Findings were robust across various sensitivity analyses, supporting the absence of pleiotropy and outliers. No reverse causality was found, indicating a unidirectional influence. Genetic predispositions to immune cells, plasma liposomes, and plasma metabolites significantly change the risk of developing AR. Further studies are needed to explore these associations in diverse populations and refine the underlying mechanisms.</p>