Smith, Alicia K, White, Peter D, Aslakson, Eric et al. · Pharmacogenomics · 2006 · DOI
This study looked at whether different genetic variations in the stress-response system (HPA axis) and mood-related brain chemistry might explain why ME/CFS affects people differently. Researchers identified five distinct subgroups of people with chronic fatigue and found that three of these groups had different versions of specific genes compared to healthy people, suggesting that ME/CFS may not be one disease but rather several different conditions with different underlying genetic causes.
This research demonstrates that ME/CFS is not monolithic and that different patients may have different genetic underpinnings for their illness. Understanding these genetic subtypes could lead to personalized diagnosis and treatment approaches, rather than applying one-size-fits-all interventions to a heterogeneous population.
This study does not prove that these genetic polymorphisms cause ME/CFS—it only shows associations in this particular sample. The cross-sectional design cannot establish causality, and the findings require replication in larger, independent populations before conclusions about genetic causation can be drawn.
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
Smith, Alicia K, White, Peter D, Aslakson, Eric, Vollmer-Conna, Ute, & Rajeevan, Mangalathu S (2006). Polymorphisms in genes regulating the HPA axis associated with empirically delineated classes of unexplained chronic fatigue.. Pharmacogenomics. https://doi.org/10.2217/14622416.7.3.387
BibTeX
@article{mecfsatlas-smith-2006-polymorphisms-genes,
author = {Smith, Alicia K and White, Peter D and Aslakson, Eric and Vollmer-Conna, Ute and Rajeevan, Mangalathu S},
title = {Polymorphisms in genes regulating the HPA axis associated with empirically delineated classes of unexplained chronic fatigue.},
journal = {Pharmacogenomics},
year = {2006},
doi = {10.2217/14622416.7.3.387},
note = {PubMed: 16610949},
url = {https://www.mecfsatlas.com/evidence/smith-2006-polymorphisms-genes},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-28. https://www.mecfsatlas.com/evidence/smith-2006-polymorphisms-genes
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