Ruseva, Albena G, Valencia, Braulio M, Gordon, Scott D et al. · Twin research and human genetics : the official journal of the International Society for Twin Studies · 2026 · DOI
Researchers studied whether genetic risk for depression or chronic fatigue could predict who would develop a fatigue syndrome after infection. In a group of 464 people followed after confirmed infection, they observed that neither depression genetics nor chronic fatigue genetics were associated with developing this condition overall—though a preliminary finding suggested depression genetics might affect risk differently in women versus men. These early results suggest genetic liability to depression or chronic fatigue alone may not be the main driver of postinfective fatigue syndrome.
By analogy, this finding may be relevant to understanding ME/CFS pathogenesis: if common genetic liability to depression does not predict postinfective fatigue syndrome, it suggests psychological factors or pre-existing affective risk may play a more limited role than historically debated. The exploratory sex-dependent signal, should it replicate, could inform whether biological sex influences how genetic and environmental risk factors converge in postinfective fatigue states that meet ME/CFS criteria.
This study does not establish that depression or fatigue genetics *cause* or *protect against* PIFS; it reports associations only. The exploratory sex-by-PGS interaction was underpowered and suggestive, not confirmatory, and does not generalise beyond this cohort until replicated. Absence of association does not rule out rare-variant genetic contributions or gene-by-environment interactions. The relevance of these findings to ME/CFS cases arising from other infection types or in other populations remains unclear.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Ruseva, Albena G, Valencia, Braulio M, Gordon, Scott D, Lloyd, Andrew, Hickie, Ian B, & Martin, Nicholas (2026). Can Depression Polygenic Risk Score Predict Postinfective Fatigue Syndrome (PIFS) in the Dubbo Infection Outcomes Study (DIOS)?. Twin research and human genetics : the official journal of the International Society for Twin Studies. https://doi.org/10.1017/thg.2026.10098
BibTeX
@article{mecfsatlas-ruseva-2026-can-depression,
author = {Ruseva, Albena G and Valencia, Braulio M and Gordon, Scott D and Lloyd, Andrew and Hickie, Ian B and Martin, Nicholas},
title = {Can Depression Polygenic Risk Score Predict Postinfective Fatigue Syndrome (PIFS) in the Dubbo Infection Outcomes Study (DIOS)?},
journal = {Twin research and human genetics : the official journal of the International Society for Twin Studies},
year = {2026},
doi = {10.1017/thg.2026.10098},
note = {PubMed: 42773889},
url = {https://www.mecfsatlas.com/evidence/ruseva-2026-can-depression},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-09-24. https://www.mecfsatlas.com/evidence/ruseva-2026-can-depression
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