A Mendelian randomization study: causal relationship between immune cells and the risks of social phobia, specific phobia, and agoraphobia

Abstract Background Although phobia is a common psychiatric disorder, the underlying biological mechanisms have not been fully elucidated. Complex immune-brain interactions that affect neural development, survival, and function may have causal and therapeutic implications in psychiatric illnesses. I...

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Main Authors: Jun-Neng Wang, Dong-Hu Yu, Zhi-Yu Li, Ling-Yue Kong, Nan-Hao Li, You-Xian Wu, Tian-Qing Wang, Ze-Fen Wang, Zhi-Qiang Li
Format: Article
Language:English
Published: BMC 2025-04-01
Series:BMC Psychiatry
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Online Access:https://doi.org/10.1186/s12888-025-06794-4
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author Jun-Neng Wang
Dong-Hu Yu
Zhi-Yu Li
Ling-Yue Kong
Nan-Hao Li
You-Xian Wu
Tian-Qing Wang
Ze-Fen Wang
Zhi-Qiang Li
author_facet Jun-Neng Wang
Dong-Hu Yu
Zhi-Yu Li
Ling-Yue Kong
Nan-Hao Li
You-Xian Wu
Tian-Qing Wang
Ze-Fen Wang
Zhi-Qiang Li
author_sort Jun-Neng Wang
collection DOAJ
description Abstract Background Although phobia is a common psychiatric disorder, the underlying biological mechanisms have not been fully elucidated. Complex immune-brain interactions that affect neural development, survival, and function may have causal and therapeutic implications in psychiatric illnesses. In this study, the relationships between immune cell traits and phobia were analysed using Mendelian randomization to explore the biological mechanisms. Methods Based on publicly-available genetic data, a two-sample MR analysis was used to determine the causal relationship between 731 immune cell traits and the risk of developing phobias. Sensitivity analyses were conducted to verify the robustness, heterogeneity, and horizontal pleiotropy of the results. Results After forward and reverse analyses, false discovery rate (FDR) corrections were performed. No significant associations between phobias and immune cell traits were identified. After adjusting the FDR threshold, social phobia affected two immune cell traits: CD39 on granulocytes (β = 9.0347, 95% confidence interval (CI) = 4.4802–13.5891, P = 0.0001, FDR = 0.0738), and CD11c on granulocytes (β = 7.7976, 95% CI = 3.4616–12.1336, P = 0.0004, FDR = 0.1547). Three immune cell traits affected the risk of specific phobias: CD4 + CD8dim T cell %leukocyte (odds ratio (OR) = 0.9985, 95% CI = 0.9976–0.9993, P = 0.0006, FDR = 0.1373), CD45 on CD33 + HLA DR + CD14dim (OR = 0.9977, 95% CI = 0.9964–0.9990, P = 0.0004, FDR = 0.1373), and CD8 on CD28 + CD45RA + CD8br (OR = 0.9990, 95% CI = 0.9985–0.9996, P = 0.0003, FDR = 0.1373). Two immune cell traits affected the risk of agoraphobia: CD3 on CD39 + resting regulatory T cells (Tregs) (OR = 1.0010, 95 CI%=1.0005–1.0015, P = 0.0001, FDR = 0.0596) and HLA DR on CD33br HLA DR + CD14dim (OR = 0.9993, 95 CI%=0.9990–0.9997, P = 0.0002, FDR = 0.0596). Conclusions Immune cell traits closely related to phobias were screened out through genomics, which provides a reference for the subsequent research on the immune system-phobia interaction.
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spelling doaj-art-12b660dce9fa4f8f8dc79d4df997d0b82025-08-20T02:17:02ZengBMCBMC Psychiatry1471-244X2025-04-012511710.1186/s12888-025-06794-4A Mendelian randomization study: causal relationship between immune cells and the risks of social phobia, specific phobia, and agoraphobiaJun-Neng Wang0Dong-Hu Yu1Zhi-Yu Li2Ling-Yue Kong3Nan-Hao Li4You-Xian Wu5Tian-Qing Wang6Ze-Fen Wang7Zhi-Qiang Li8Brain Glioma Center & Department of Neurosurgery, Zhongnan Hospital of Wuhan UniversityBrain Glioma Center & Department of Neurosurgery, Zhongnan Hospital of Wuhan UniversityBrain Glioma Center & Department of Neurosurgery, Zhongnan Hospital of Wuhan UniversityBrain Glioma Center & Department of Neurosurgery, Zhongnan Hospital of Wuhan UniversityBrain Glioma Center & Department of Neurosurgery, Zhongnan Hospital of Wuhan UniversityBrain Glioma Center & Department of Neurosurgery, Zhongnan Hospital of Wuhan UniversityBrain Glioma Center & Department of Neurosurgery, Zhongnan Hospital of Wuhan UniversityDepartment of Physiology, Wuhan University School of Basic Medical SciencesBrain Glioma Center & Department of Neurosurgery, Zhongnan Hospital of Wuhan UniversityAbstract Background Although phobia is a common psychiatric disorder, the underlying biological mechanisms have not been fully elucidated. Complex immune-brain interactions that affect neural development, survival, and function may have causal and therapeutic implications in psychiatric illnesses. In this study, the relationships between immune cell traits and phobia were analysed using Mendelian randomization to explore the biological mechanisms. Methods Based on publicly-available genetic data, a two-sample MR analysis was used to determine the causal relationship between 731 immune cell traits and the risk of developing phobias. Sensitivity analyses were conducted to verify the robustness, heterogeneity, and horizontal pleiotropy of the results. Results After forward and reverse analyses, false discovery rate (FDR) corrections were performed. No significant associations between phobias and immune cell traits were identified. After adjusting the FDR threshold, social phobia affected two immune cell traits: CD39 on granulocytes (β = 9.0347, 95% confidence interval (CI) = 4.4802–13.5891, P = 0.0001, FDR = 0.0738), and CD11c on granulocytes (β = 7.7976, 95% CI = 3.4616–12.1336, P = 0.0004, FDR = 0.1547). Three immune cell traits affected the risk of specific phobias: CD4 + CD8dim T cell %leukocyte (odds ratio (OR) = 0.9985, 95% CI = 0.9976–0.9993, P = 0.0006, FDR = 0.1373), CD45 on CD33 + HLA DR + CD14dim (OR = 0.9977, 95% CI = 0.9964–0.9990, P = 0.0004, FDR = 0.1373), and CD8 on CD28 + CD45RA + CD8br (OR = 0.9990, 95% CI = 0.9985–0.9996, P = 0.0003, FDR = 0.1373). Two immune cell traits affected the risk of agoraphobia: CD3 on CD39 + resting regulatory T cells (Tregs) (OR = 1.0010, 95 CI%=1.0005–1.0015, P = 0.0001, FDR = 0.0596) and HLA DR on CD33br HLA DR + CD14dim (OR = 0.9993, 95 CI%=0.9990–0.9997, P = 0.0002, FDR = 0.0596). Conclusions Immune cell traits closely related to phobias were screened out through genomics, which provides a reference for the subsequent research on the immune system-phobia interaction.https://doi.org/10.1186/s12888-025-06794-4Social phobiaSpecific phobiaAgoraphobiaImmunityMendelian randomization
spellingShingle Jun-Neng Wang
Dong-Hu Yu
Zhi-Yu Li
Ling-Yue Kong
Nan-Hao Li
You-Xian Wu
Tian-Qing Wang
Ze-Fen Wang
Zhi-Qiang Li
A Mendelian randomization study: causal relationship between immune cells and the risks of social phobia, specific phobia, and agoraphobia
BMC Psychiatry
Social phobia
Specific phobia
Agoraphobia
Immunity
Mendelian randomization
title A Mendelian randomization study: causal relationship between immune cells and the risks of social phobia, specific phobia, and agoraphobia
title_full A Mendelian randomization study: causal relationship between immune cells and the risks of social phobia, specific phobia, and agoraphobia
title_fullStr A Mendelian randomization study: causal relationship between immune cells and the risks of social phobia, specific phobia, and agoraphobia
title_full_unstemmed A Mendelian randomization study: causal relationship between immune cells and the risks of social phobia, specific phobia, and agoraphobia
title_short A Mendelian randomization study: causal relationship between immune cells and the risks of social phobia, specific phobia, and agoraphobia
title_sort mendelian randomization study causal relationship between immune cells and the risks of social phobia specific phobia and agoraphobia
topic Social phobia
Specific phobia
Agoraphobia
Immunity
Mendelian randomization
url https://doi.org/10.1186/s12888-025-06794-4
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