Causal relationship between inflammatory cytokines and posttraumatic stress disorder: a Mendelian randomization study and potential mechanism analysis

Background: Post-traumatic stress disorder (PTSD) is a complex condition linked to inflammation. The causality between inflammatory cytokines and PTSD risk remains unclear.Methods: We conducted a bidirectional two-sample Mendelian randomization (MR) study using genome-wide association study (GWAS) d...

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Main Authors: Yingchong Li, Bangliang Xu, Zhitao Chen
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:European Journal of Psychotraumatology
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Online Access:https://www.tandfonline.com/doi/10.1080/20008066.2025.2494480
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author Yingchong Li
Bangliang Xu
Zhitao Chen
author_facet Yingchong Li
Bangliang Xu
Zhitao Chen
author_sort Yingchong Li
collection DOAJ
description Background: Post-traumatic stress disorder (PTSD) is a complex condition linked to inflammation. The causality between inflammatory cytokines and PTSD risk remains unclear.Methods: We conducted a bidirectional two-sample Mendelian randomization (MR) study using genome-wide association study (GWAS) data from 41 inflammatory cytokines and PTSD. Additional analyses included differential gene expression, protein–protein interaction, and functional enrichment to explore underlying mechanisms.Results: MR analysis indicated that higher levels of stem cell factor (SCF) and interleukin-4 (IL-4) are associated with a reduced risk of PTSD. Genes POGZ and LRIG2 were identified as mediators, implicated in the TGF-beta signalling pathway.Conclusion: Our findings suggest a protective role of certain cytokines against PTSD and highlight potential molecular mediators. This knowledge could inform future therapeutic strategies for PTSD.
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publisher Taylor & Francis Group
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series European Journal of Psychotraumatology
spelling doaj-art-7c1fb2532e224519bdc5fb8d1e7993b82025-08-20T03:52:07ZengTaylor & Francis GroupEuropean Journal of Psychotraumatology2000-80662025-12-0116110.1080/20008066.2025.2494480Causal relationship between inflammatory cytokines and posttraumatic stress disorder: a Mendelian randomization study and potential mechanism analysisYingchong Li0Bangliang Xu1Zhitao Chen2National Clinical Research Center for Child Health, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaNational Clinical Research Center for Child Health, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaShulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, People’s Republic of ChinaBackground: Post-traumatic stress disorder (PTSD) is a complex condition linked to inflammation. The causality between inflammatory cytokines and PTSD risk remains unclear.Methods: We conducted a bidirectional two-sample Mendelian randomization (MR) study using genome-wide association study (GWAS) data from 41 inflammatory cytokines and PTSD. Additional analyses included differential gene expression, protein–protein interaction, and functional enrichment to explore underlying mechanisms.Results: MR analysis indicated that higher levels of stem cell factor (SCF) and interleukin-4 (IL-4) are associated with a reduced risk of PTSD. Genes POGZ and LRIG2 were identified as mediators, implicated in the TGF-beta signalling pathway.Conclusion: Our findings suggest a protective role of certain cytokines against PTSD and highlight potential molecular mediators. This knowledge could inform future therapeutic strategies for PTSD.https://www.tandfonline.com/doi/10.1080/20008066.2025.2494480Post-traumatic stress disorderinflammatory cytokinesstem cell factorinterleukin-4Mendelian randomizationgenome-wide association study
spellingShingle Yingchong Li
Bangliang Xu
Zhitao Chen
Causal relationship between inflammatory cytokines and posttraumatic stress disorder: a Mendelian randomization study and potential mechanism analysis
European Journal of Psychotraumatology
Post-traumatic stress disorder
inflammatory cytokines
stem cell factor
interleukin-4
Mendelian randomization
genome-wide association study
title Causal relationship between inflammatory cytokines and posttraumatic stress disorder: a Mendelian randomization study and potential mechanism analysis
title_full Causal relationship between inflammatory cytokines and posttraumatic stress disorder: a Mendelian randomization study and potential mechanism analysis
title_fullStr Causal relationship between inflammatory cytokines and posttraumatic stress disorder: a Mendelian randomization study and potential mechanism analysis
title_full_unstemmed Causal relationship between inflammatory cytokines and posttraumatic stress disorder: a Mendelian randomization study and potential mechanism analysis
title_short Causal relationship between inflammatory cytokines and posttraumatic stress disorder: a Mendelian randomization study and potential mechanism analysis
title_sort causal relationship between inflammatory cytokines and posttraumatic stress disorder a mendelian randomization study and potential mechanism analysis
topic Post-traumatic stress disorder
inflammatory cytokines
stem cell factor
interleukin-4
Mendelian randomization
genome-wide association study
url https://www.tandfonline.com/doi/10.1080/20008066.2025.2494480
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AT bangliangxu causalrelationshipbetweeninflammatorycytokinesandposttraumaticstressdisorderamendelianrandomizationstudyandpotentialmechanismanalysis
AT zhitaochen causalrelationshipbetweeninflammatorycytokinesandposttraumaticstressdisorderamendelianrandomizationstudyandpotentialmechanismanalysis