Immune Cells, Metabolites, and Intracranial Aneurysms: A Mendelian Randomization Study

Introduction: The authors' aim is to comprehensively investigate the causal relationship between 731 immune cell traits and intracranial aneurysms (IAs), and to identify and quantify the role of 1400 metabolic traits as potential mediators in the association between the two. Methods: Using summary data from genome-wide association studies (GWAS), the authors conducted a 2-sample bidirectional Mendelian randomization (MR) analysis for 731 immune cell traits and genetically predicted IAs. Emphatically, the authors used a 2-step MR analysis to quantify the proportion of the total effect mediated by potential metabolites on the impact of immune cells on IAs risk. Results: The authors identified 23 immune cells [with odds ratio (OR) ranging from 1.2147 to 0.8962] and 13 metabolic traits (with OR ranging from 1.4866 to 0.7783) that have a causal relationship with AIT. Five immune cells (including IgD- CD38din% B cell, CD25 on CD39+ CD4+ T cell, BAFF-R on memory B cell, SSC-A on monocyte, CD27 on CD20− CD38− B cell) were found to be associated with the risk of IAs, partially mediated by 6 metabolites (1,2-dipalmitoyl-gpc (16:0/16:0), X-11478, (N(1) + N(8))-acetylspermidine, Sphingomyelin (d18:1/22:2, d18:2/22:1, d16:1/24:2), Retinol to linoleoyl-arachidonoyl-glycerol (18:2–20:4) ratio, Cholesterol to linoleoylarachidonoyl-glycerol (18:2–20:4) ratio). The proportion of genetically predicted IAs mediated by the identified metabolites ranged from −25.7% to 26.4%. Discussion: The authors' study has established causal relationships between IAs and immune cells, which are partially mediated by metabolites, thereby providing guidance for future clinical and basic research.