Revealing putative causal genes by establishing the causality between different lymphomas and immune cells

Background: The immune microenvironment not only plays a pivotal role in the pathogenesis of lymphoma but also serves as a critical determinant influencing disease progression and treatment resistance. However, there remains a dearth of comprehensive investigations exploring the causal relationship between various immune cell types and different lymphomas. Method: In this study, we employed common bidirectional two-sample mendelian randomization (MR) and linked disequilibrium score regression (LDSC) to investigate the causal relationship and genetic correlation between immune cells and various lymphomas. Additionally, we utilized the Mendelian randomization-based method of summary data-based MR (SMR), which incorporated genome-wide association studies (GWAS) and expression quantitative trait loci (eQTL) data from immune cells to identify genes associated with lymphoma. Furthermore, colocalization analysis and genetic correlation analysis were conducted for further validation of our findings. Results: The two-sample mendelian randomization approach was employed to identify the immune cell types that exhibit a causal relationship with different lymphomas. Additionally, the genetic correlation between these immune cells and malignant lymphomas was further analyzed using the linked disequilibrium score regression method, thereby enhancing the reliability of our findings. The SMR and colocalization analyses revealed several genes associated with these immune cells, thereby providing additional support for their putative role in the pathogenesis of lymphoma. Conclusions: Our study elucidates the intricate interplay between immune cells by employing genetic methodologies, thus offering insights for potential therapeutic targets and risk predictors in different subtypes of lymphoma treatments.