Plasma lipidomes, immune cells, and headaches induced by sinusitis: a bidirectional Mendelian randomization studypotential

Background: Chronic rhinosinusitis (CRS) is a complex disease influenced by various factors such as environmental exposure, microbial infection, immune dysfunction, and genetic predisposition. The objective of this research is to examine the causal relationship between plasma lipidomes and CRS, focusing on the potential role of immune cells as mediators.Methods: Utilizing pooled data from genome-wide association studies (GWAS), a two-sample Mendelian randomization (MR) analysis was conducted to investigate the causal relationship between genetically predicted plasma lipidomes (7174 cases) and CRS (7529 cases, 444966 controls). Various methods such as inverse variance weighted, maximum likelihood, MR-Egger, weighted median, weighted mode, and Wald ratio were employed to assess causality. Multiple sensitivity analyses were also conducted to ensure the reliability of the MR results. Furthermore, mediation analysis was used to identify immune cell-mediated pathways linking plasma lipidomes to chronic sinusitis.Results: The study identified 30 plasma lipidomes associated with chronic sinusitis, with only one remaining significant after FDR correction, namely Phosphatidylinositol (18:1_18:2). Additionally, 52 types of immune cells were found to be related to the disease, with only 3 types remaining significant after FDR correction: CD27+/IgD- CD38+ B cells, CD3+/CD28+ CD4+ T cells, and HLA DR+/CD33+ HLA DR+ CD14- cells. Mediation analysis revealed two distinct mediating relationships, indicating potential pathways from plasma lipidomes to chronic sinusitis through two specific immune cells. Sensitivity analysis results indicated no heterogeneity or pleiotropy in the study.Conclusion: The findings of this study reinforce the causal link between plasma lipidomes, immune cells, and chronic sinusitis. Identifying these biomarkers offers fresh insights into the pathogenesis of chronic sinusitis, with implications for improved prevention, diagnosis, and treatment of the condition.