The Genetic Link Between Primary Immune Thrombocytopenia and Depression/Anxiety Disorders: A Two‐Sample Mendelian Randomization Study

BACKGROUND: Primary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with complex immunopathogenesis. Its major symptoms, such as bleeding tendency and fatigue, may predispose patients to depression and anxiety. Although psychiatric comorbidities are increasingly recognized in ITP management, whether ITP causally contributes to these conditions remains unclear. METHODS: We conducted a two-sample Mendelian randomization (MR) study to investigate the potential genetically causal links between ITP and depression/anxiety. To ensure robustness, complementary MR approaches were performed, including pleiotropy-robust methods (MR-Corr and MRMix), multivariable MR adjusting for inflammatory biomarkers (C-reactive protein and interleukin-6), the robust adjusted profile score (RAPS) model, reverse MR, and colocalization analysis. RESULTS: MR analysis revealed a positive causal effect of ITP on depression (OR = 1.007, 95% CI: 1.001-1.013; p = 0.014), whereas no genetic predisposition of ITP on anxiety was observed. Multivariable and pleiotropy-robust sensitivity analyses supported the stability and consistency of the ITP-depression association, indicating that the result was unlikely driven by pleiotropy, instrument weakness, or inflammatory confounding. CONCLUSION: These findings provided novel genetic evidence supporting ITP-associated mental health issues and highlighted the importance of integrated psycho-hematological interventions for ITP in clinical practice. Future research was needed to elucidate the biological underpinning between ITP and psychiatric disorders, which might provide more options for ITP patients to improve life quality.