The causal relationship between inflammatory cytokines and thrombocytopenia: A bidirectional two-sample Mendelian randomization study

Abstract

Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease characterized by increased platelet destruction and impaired thrombopoiesis. Epidemiological and experimental evidence has linked inflammation cytokine levels to ITP etiology but is uncertain. To respond to this query, we conducted a Mendelian randomization (MR) analysis to investigate the causal effects of circulating cytokine levels on ITP development. Using summary statistics from genome-wide association studies (GWAS), we obtained data on 41 serum cytokines from 8,293 Finnish individuals and ITP data from a meta-analysis of the FinnGen consortium, UK Biobank, and BioBank Japan. The association between genetically predicted levels of inflammatory cytokines and ITP was estimated using a bidirectional Mendelian randomization (MR) study. Sensitivity analyses and the False Discovery Rate (FDR) method were also performed to verify the robustness of the results. We discovered that higher genetically predicted M-CSF levels were strongly associated with an increased risk of ITP (OR: 1.09; 95%CI: 1.03–1.16; p = 0.003) and gestational thrombocytopenia (GT) (OR: 1.17; 95%CI, 1.05–1.32; p = 0.006). Additionally, our results showed an adverse association between genetically predicted levels of the circulating HGF (OR: 0.75; 95%CI, 0.63–0.90; p = 0.002), MIF (OR: 0.90; 95%CI, 0.84–0.96; p = 0.001) and TRAIL (OR: 0.92; 95%CI, 0.87–0.97; p = 0.003) with the GT. The study result links genetic predisposition to elevated M-CSF levels with increased risks of ITP and GT, suggesting that targeting cytokines could aid in ITP prevention, though further validation is needed.