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...

Full description

Saved in:
Bibliographic Details
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
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2045-2322