Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jan 9:14:1338083.
doi: 10.3389/fimmu.2023.1338083. eCollection 2023.

Causal role of immune cells in generalized anxiety disorder: Mendelian randomization study

Zhen Ma  1 , Min Zhao  1 , Huanghong Zhao  2 , Nan Qu  1
Affiliations

Causal role of immune cells in generalized anxiety disorder: Mendelian randomization study

Zhen Ma et al. Front Immunol. .

Abstract

Background: Generalized anxiety disorder (GAD) is a prevalent emotional disorder that has received relatively little attention regarding its immunological basis. Recent years have seen the widespread use of high-density genetic markers such as SNPs or CNVs for genotyping, as well as the advancement of genome-wide association studies (GWAS) technologies, which have facilitated the understanding of immunological mechanisms underlying several major psychiatric disorders. Despite these advancements, the immunological basis of GAD remains poorly understood. In light of this, we aimed to explore the causal relationship between immune cells and the disease through a Mendelian randomization study.

Methods: The summary information for GAD (Ncase=4,666, Ncontrol=337,577) was obtained from the FinnGen dataset. Summary statistics for the characterization of 731 immune cells, including morphological parameters (MP=32), median fluorescence intensity (MFI=389), absolute cells (AC=118), and relative cells (RC=192), were derived from the GWAS catalog. The study involved both forward MR analysis, with immune cell traits as the exposure and GAD as the outcome, and reverse MR analysis, with GAD as the exposure and immune cell traits as the outcome. We performed extensive sensitivity analyses to confirm the robustness, heterogeneity, and potential multi-biological effects of the study results. Also, to control for false positive results during multiple hypothesis testing, we adopted a false discovery rate (FDR) to control for statistical bias due to multiple comparisons.

Results: After FDR correction, GAD had no statistically significant effect on immunophenotypes. Several phenotypes with unadjusted low P-values are worth mentioning, including decreased PB/PC levels on B cells(β=-0.289, 95%CI=0.044~0.194, P=0.002), reduced PB/PC AC in GAD patients (β=-0.270, 95% CI=0.77~0.92, P=0.000), and diminished PB/PC on lymphocytes (β=-0.315, 95% CI=0.77~0.93, P=0.001). GAD also exerted a causal effect on CD27 on IgD-CD38br (β=-0.155,95%CI=0.78~0.94,P=0.002), CD20-%B cell (β= -0.105,95% CI=0.77~0.94, P=0.002), IgD-CD38br%lymphocyte(β=-0.305, 95%CI=0.79~0.95, P=0.002), FSC-A level on granulocytes (β=0.200, 95%CI=0.75~0.91, P=8.35×10-5), and CD4RA on TD CD4+(β=-0.150, 95% CI=0.82~1.02, P=0.099). Furthermore, Two lymphocyte subsets were identified to be significantly associated with GAD risk: CD24+ CD27+ B cell (OR=1.066,95%CI=1.04~1.10,P=1.237×10-5),CD28+CD4+T cell (OR=0.927, 95%CI=0.89~0.96, P=8.085×10-5).

Conclusion: The study has shown the close association between immune cells and GAD through genetic methods, thereby offering direction for future clinical research.

Keywords: MR analysis; causal inference; generalized anxiety disorder; immunity; sensitivity.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Overview of this bidirectional MR study design.
Figure 2
Figure 2
Forest plots showed the causal relations between GAD and immune cell traits.
Figure 3
Figure 3
Forest plots showed the causal associations between immune cell traits and GAD by using different methods.
See this image and copyright information in PMC

References

    1. Das A, Clerkin EM, Tolin DF, Assaf M, Diefenbach GJ. Moving beyond the negative: contributions of positive and negative affect on quality of life in patients with generalized anxiety disorder. J Nerv Ment Dis (2020) 208(11):843–7. doi: 10.1097/NMD - DOI - PubMed
    1. Showraki M, Showraki T, Brown K. Generalized anxiety disorder: revisited. Psychiatr Q (2020) 91(3):905–14. doi: 10.1007/s11126-020-09747-0 - DOI - PubMed
    1. Mohammadi MR, Pourdehghan P, Mostafavi SA, Hooshyari Z, Ahmadi N, Khaleghi A. Generalized anxiety disorder: Prevalence, predictors, and comorbidity in children and adolescents. J Anxiety Disord (2020) 73:102234. doi: 10.1016/j.janxdis.2020.102234 - DOI - PubMed
    1. Hurtado MM, Nogueras EV, Cantero N, Gálvez L, García-Herrera JM, Morales-Asencio JM. Development of a guideline for the treatment of generalized anxiety disorder with the ADAPTE method. Int J Qual Health Care (2020) 32(6):356–63. doi: 10.1093/intqhc/mzaa053 - DOI - PubMed
    1. Kuang N, Liu Z, Yu G, Wu X, Becker B, Fan H, et al. . Neurodevelopmental risk and adaptation as a model for comorbidity among internalizing and externalizing disorders: genomics and cell-specific expression enriched morphometric study. BMC Med (2023) 21(1):291. doi: 10.1186/s12916-023-02920-9 - DOI - PMC - PubMed

Publication types