Abstract
BACKGROUND: This study investigates the causal relationships between 731 immune cell traits and aortic dissection (AD) using Mendelian randomisation (MR). By identifying specific immune cell phenotypes contributing to AD, we explore their clinical implications for risk stratification and therapeutic interventions. METHODS: A bivariate MR framework analysed the causal dynamics between immune cell attributes and AD, using genetic variants as instrumental variables. Summary statistics from a genome-wide association study for 731 immune phenotypes were obtained. Univariable MR analysis was conducted using the inverse-variance weighted method supplemented by sensitivity analyses. Horizontal pleiotropy was assessed using MR-Egger and MR pleiotropy residual sum and outlier. Significant cis-expression quantitative trait loci (eQTL) were identified via the Genotype-Tissue Expression (GTEx) database, followed by tissue-specific expression and pathway analyses. RESULTS: Four immunophenotypes exhibited positive causal effects on AD, while one showed a negative effect. Pathogenic traits included the median fluorescence intensity of CD19 on transitional B cells, immunoglobulin D(-) CD38dim B cells, CD3 on CD39(+) CD4(+) Treg cells, and CD3 on CD39(+) activated Treg cells. The protective trait was the absolute count of CD86(+) myeloid dendritic cells. Sensitivity analyses validated these associations. Pathway enrichment analysis highlighted significant arterial enrichments and key biological processes, identifying SLAMF6 and CD28 as key genes. CONCLUSION: This study suggests potential causal roles for specific immune cell traits in AD pathogenesis, although these findings should be interpreted with caution due to study limitations. The identified immune cell types and associated eQTL genes offer promising targets for clinical risk stratification and therapeutic interventions. Future research should focus on translating these findings into practical strategies for patient care.