Relationship between major depressive disorder and myalgic encephalomyelitis/chronic fatigue syndrome: a two-sample mendelian randomization study analysis

Abstract Major depressive disorder (MDD) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) frequently occur together; yet their causal relationship remains unclear. To investigate the potential genetic causal link between these conditions, we conducted a two-sample Mendelian randomizat...

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Main Authors: Wenjing Song, Xinlei Hou, Minmin Wu, Luwen Zhu
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-85217-6
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author Wenjing Song
Xinlei Hou
Minmin Wu
Luwen Zhu
author_facet Wenjing Song
Xinlei Hou
Minmin Wu
Luwen Zhu
author_sort Wenjing Song
collection DOAJ
description Abstract Major depressive disorder (MDD) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) frequently occur together; yet their causal relationship remains unclear. To investigate the potential genetic causal link between these conditions, we conducted a two-sample Mendelian randomization (MR) analysis. Summary data from Genome-Wide Association Studies (GWAS) for MDD were sourced from the UK Biobank and the Psychiatric Genomics Consortium, while GWAS data for ME/CFS were retrieved from the UK Biobank. Inverse-variance weighting (IVW), the MR-Egger method, and weighted median, simple and weighted modes were used to perform the MR analysis. In addition, Cochrane’s Q-test was used to detect heterogeneity among the MR results. Horizontal pleiotropy was detected using the MR-Egger intercept and the MR pleiotropy residual sum and outlier (MR-PRESSO) tests. Leave-one-out analysis was performed to investigate the sensitivity of the association between MDD and ME/CFS. The results of the MR analysis revealed no causal relationship between MDD and ME/CFS. The pleiotropy test revealed that causality bias was improbable, and no evidence of heterogeneity was found among the genetic variants. Finally, the leave-one-out test confirmed the stability and robustness of our findings.
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spelling doaj-art-1f86cb6c7fe4420482b3b671a8d903012025-08-20T02:40:35ZengNature PortfolioScientific Reports2045-23222025-01-011511610.1038/s41598-025-85217-6Relationship between major depressive disorder and myalgic encephalomyelitis/chronic fatigue syndrome: a two-sample mendelian randomization study analysisWenjing Song0Xinlei Hou1Minmin Wu2Luwen Zhu3Heilongjiang University of Chinese MedicineSecond Affiliated Hospital of Heilongjiang University of Chinese MedicineHeilongjiang University of Chinese MedicineSecond Affiliated Hospital of Heilongjiang University of Chinese MedicineAbstract Major depressive disorder (MDD) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) frequently occur together; yet their causal relationship remains unclear. To investigate the potential genetic causal link between these conditions, we conducted a two-sample Mendelian randomization (MR) analysis. Summary data from Genome-Wide Association Studies (GWAS) for MDD were sourced from the UK Biobank and the Psychiatric Genomics Consortium, while GWAS data for ME/CFS were retrieved from the UK Biobank. Inverse-variance weighting (IVW), the MR-Egger method, and weighted median, simple and weighted modes were used to perform the MR analysis. In addition, Cochrane’s Q-test was used to detect heterogeneity among the MR results. Horizontal pleiotropy was detected using the MR-Egger intercept and the MR pleiotropy residual sum and outlier (MR-PRESSO) tests. Leave-one-out analysis was performed to investigate the sensitivity of the association between MDD and ME/CFS. The results of the MR analysis revealed no causal relationship between MDD and ME/CFS. The pleiotropy test revealed that causality bias was improbable, and no evidence of heterogeneity was found among the genetic variants. Finally, the leave-one-out test confirmed the stability and robustness of our findings.https://doi.org/10.1038/s41598-025-85217-6
spellingShingle Wenjing Song
Xinlei Hou
Minmin Wu
Luwen Zhu
Relationship between major depressive disorder and myalgic encephalomyelitis/chronic fatigue syndrome: a two-sample mendelian randomization study analysis
Scientific Reports
title Relationship between major depressive disorder and myalgic encephalomyelitis/chronic fatigue syndrome: a two-sample mendelian randomization study analysis
title_full Relationship between major depressive disorder and myalgic encephalomyelitis/chronic fatigue syndrome: a two-sample mendelian randomization study analysis
title_fullStr Relationship between major depressive disorder and myalgic encephalomyelitis/chronic fatigue syndrome: a two-sample mendelian randomization study analysis
title_full_unstemmed Relationship between major depressive disorder and myalgic encephalomyelitis/chronic fatigue syndrome: a two-sample mendelian randomization study analysis
title_short Relationship between major depressive disorder and myalgic encephalomyelitis/chronic fatigue syndrome: a two-sample mendelian randomization study analysis
title_sort relationship between major depressive disorder and myalgic encephalomyelitis chronic fatigue syndrome a two sample mendelian randomization study analysis
url https://doi.org/10.1038/s41598-025-85217-6
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