Song Wenjing, Hou Xinlei, Wu Minmin, Zhu Luwen
Heilongjiang University of Chinese Medicine, Harbin, China.
Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, 411 Guogeli Street, Nangang District, Heilongjiang, Harbin, 150001, China.
Sci Rep. 2025 Jan 7;15(1):1155. doi: 10.1038/s41598-025-85217-6.
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.
重度抑郁症（MDD）和肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）经常同时出现；然而它们之间的因果关系仍不清楚。为了研究这些病症之间潜在的遗传因果联系，我们进行了一项两样本孟德尔随机化（MR）分析。MDD的全基因组关联研究（GWAS）汇总数据来自英国生物银行和精神疾病基因组学联盟，而ME/CFS的GWAS数据则从英国生物银行获取。采用逆方差加权（IVW）、MR-Egger方法以及加权中位数、简单和加权模式进行MR分析。此外，使用Cochrane的Q检验来检测MR结果之间的异质性。利用MR-Egger截距和MR多效性残差总和及异常值（MR-PRESSO）检验来检测水平多效性。进行留一法分析以研究MDD与ME/CFS之间关联的敏感性。MR分析结果显示MDD与ME/CFS之间不存在因果关系。多效性检验表明因果偏差不太可能存在，并且在基因变异中未发现异质性证据。最后，留一法检验证实了我们研究结果的稳定性和稳健性。
