Exploring causal relationship between 41 inflammatory cytokines and marginal zone lymphoma: A bidirectional Mendelian randomization study

TL;DR

This study uses genetic data to explore how 41 inflammatory cytokines are causally linked to marginal zone lymphoma, identifying potential biomarkers for diagnosis and treatment.

Contribution

The study introduces a bidirectional Mendelian randomization approach to uncover novel causal relationships between inflammatory cytokines and marginal zone lymphoma.

Findings

Elevated MIG and IL-10 levels increase the risk of marginal zone lymphoma.

Higher B-NGF levels are protective against marginal zone lymphoma.

MZL is negatively correlated with IFN-γ levels, suggesting a downstream role in disease pathogenesis.

Abstract

Marginal zone lymphoma (MZL) is a rare subtype of non-Hodgkin lymphoma, and its diagnosis primarily relies on pathological biopsy. The study aims to investigate the causal relationships between 41 inflammatory cytokines and MZL using a two-sample bidirectional Mendelian randomization (MR) approach, providing new insights and methodologies for rapid differential diagnosis and treatment strategies.

Causal associations between 41 inflammatory cytokines and MZL were examined using genetic variant data from two large-scale genome-wide association studies. The inverse variance weighting method was employed, and multiple sensitivity analyses, including MR-Egger, weighted median, simple model, and weighted model methods, were conducted to strengthen the robustness of the findings.

Elevated levels of MIG and IL-10 were associated with an increased risk of MZL (MIG: OR = 1.57, p = 0.035; IL-10: OR = 1.69, p = 0.021), while higher B-NGF levels exhibited a protective effect (OR = 0.46, p = 0.027). Reverse MR analysis revealed a negative correlation between MZL and IFN-γ levels (OR = 0.97, p = 0.015).

MIG, IL-10, B-NGF, and IFN-γ are potential biomarkers and therapeutic targets for MZL. IFN-γ likely acts as a downstream molecule in MZL pathogenesis, offering novel insights into MZL-related research, clinical diagnosis, and treatment strategies.

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