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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cytokines and Soluble Mediators in Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1452214
This article is part of the Research Topic Unraveling the Nexus of Inflammatory Biomarkers and Cognitive Dysfunction in Schizophrenia: Implications for Treatment and Disease Progression View all 3 articles

The causal relationship between immune cell traits and schizophrenia: A Mendelian randomization analysis

Provisionally accepted
Jianbin Du Jianbin Du 1Ancha Baranova Ancha Baranova 2Guofu Zhang Guofu Zhang 1*Fuquan Zhang Fuquan Zhang 3*
  • 1 The Affiliated Mental Health Center, Jiangnan University, Wuxi, Liaoning Province, China
  • 2 School of Systems Biology, College of Science, George Mason University, Manassas, Virginia, United States
  • 3 Department of Psychiatry, Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Liaoning Province, China

The final, formatted version of the article will be published soon.

    The complex and unresolved pathogenesis of schizophrenia has posed significant challenges to its diagnosis and treatment. While recent research has established a clear association between immune function and schizophrenia, the causal relationship between the two remains elusive. In this study, we employed a bidirectional two-sample Mendelian randomization approach to investigate the causal relationship between schizophrenia and 731 immune cell traits by utilizing public GWAS data. We further validated the causal relationship between schizophrenia and six types of white cell measures. Our analysis found the overall causal effects of schizophrenia on immune cell traits were significantly higher than the reverse ones (0.011±0.049 vs 0.001±0.016, p < 0.001), implying that disease may lead to an increase in immune cells by itself. We identified four immune cell traits that may increase the risk of schizophrenia: CD11c+ monocyte %monocyte (odds ratio (OR): 1.06, 95% confidence interval (CI): 1.03~1.09, FDR = 0.027), CD11c+ CD62L- monocyte %monocyte (OR:1.06, 95% CI: 1.03~1.09, FDR = 0.027), CD25 on IgD+ CD38- naive B cell (OR:1.03, 95% CI:1.01~1.06, FDR = 0.042), and CD86 on monocyte (OR = 1.04, 95%CI:1.01~1.06, FDR = 0.042). However, we did not detect any significant causal effects of schizophrenia on immune cell traits. Using the white blood cell traits data, we identified that schizophrenia increases the lymphocyte counts (OR:1.03, 95%CI: 1.01-1.04, FDR = 0.007), total white blood cell counts (OR:1.02, 95%CI: 1.01-1.04, FDR = 0.021) and monocyte counts (OR:1.02, 95%CI: 1.00-1.03, FDR = 0.034). The lymphocyte counts were nominally associated with the risk of schizophrenia (OR:1.08,95%CI:1.01-1.16, P=0.019). In conclusion, our study found that the causal relationship between schizophrenia and the immune system is complex, enhancing our understanding of the role of immune regulation in the development of this disorder. These findings offer new insights for exploring diagnostic and therapeutic options for schizophrenia.

    Keywords: Schizophrenia, immune cell, immunology, Psychiatry, Mendelian Randomization Analysis

    Received: 20 Jun 2024; Accepted: 09 Sep 2024.

    Copyright: © 2024 Du, Baranova, Zhang and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Guofu Zhang, The Affiliated Mental Health Center, Jiangnan University, Wuxi, 214151, Liaoning Province, China
    Fuquan Zhang, Department of Psychiatry, Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, Liaoning Province, China

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