Causal role of genetically predicted 731 immune cell phenotypes in chronic lymphatic leukemia: A bidirectional Mendelian randomization study

Abstract

Introduction

The direct causal relationship between these anomalies and chronic lymphatic leukemia (CLL) remains ambiguous. This study sought to investigate the potential causal link between immune cells and CLL.

Materials and methods

The summary data for genome-wide association studies utilized in this research were sourced from various publicly accessible databases, including the GWAS and FinnGen databases. By amalgamating these extensive genetic resources, we applied an array of cutting-edge Mendelian randomization (MR) analytical techniques. Specifically, we employed the inverse variance weighting (IVW) method, the weighted median method, the MR-Egger method, the Cochran Q test, Leave-One-Out sensitivity analysis, and the weighted model method to rigorously evaluate the potential causal link between multiple immune cell phenotypes and CLL.

Results

IVW analyses consistently demonstrated significant causal associations between five groups of immune cells and CLL. These associations were observed in both forward MR analyses from immune cells to CLL, and reverse MR analyses from CLL to immune cells. The five groups of immune cells under investigation included CD14+ CD16- monocyte Absolute Count, CD4+CD8+ T cell Absolute Count, BAFF-R on IgD- CD27- B cell, HLA DR+ T cell Absolute Count, and CD4+ T cell Absolute Count. Further sensitivity analyses not only confirmed the consistency in the direction of the association but also ruled out potential heterogeneity and horizontal pleiotropy effects. This enhanced the robustness and reliability of the study findings.

Conclusion

This investigation discerned definitive causal links between five immune cell phenotypes and CLL, underscoring the pivotal role of immune cells in the pathogenesis of this disease.