Hirsch, Annemarie G, Justice, Anne E, Poissant, Amy et al. · BMC infectious diseases · 2025 · DOI
Researchers studied the genes of people who had Lyme disease to understand why some develop lasting symptoms even after treatment. They found two genetic regions that might be involved in persistent Lyme disease symptoms, with one linked to a protein called MARC2 that affects immune function. When they checked whether these same genetic changes appeared in people with fibromyalgia or ME/CFS, they did not find the same patterns, suggesting these conditions may have different genetic roots.
Although this study focuses on Lyme disease, it addresses the hypothesis that ME/CFS, fibromyalgia, and post-Lyme disease syndrome share overlapping biological mechanisms. The findings that these conditions do not share the identified genetic variants suggest ME/CFS has distinct genetic underpinnings, which could guide future research into ME/CFS-specific genetic risk factors and immune dysfunction.
This study does not prove that MARC2 or the identified variants cause PTLDS; it only identifies genetic associations that require validation in larger populations. The lack of overlap between PTLDS, fibromyalgia, and ME/CFS loci does not rule out shared non-genetic pathways (e.g., environmental triggers, infections, inflammatory cascades). Suggestive-threshold findings (P<5×10⁻⁷) fall below genome-wide significance and require replication before clinical application.
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 →
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Primary citation
Hirsch, Annemarie G, Justice, Anne E, Poissant, Amy, Nordberg, Cara M, Josyula, Navya S, Aucott, John, et al. (2025). A comparison of genome-wide association analyses of persistent symptoms after Lyme disease, fibromyalgia, and myalgic encephalomyelitis - chronic fatigue syndrome.. BMC infectious diseases. https://doi.org/10.1186/s12879-024-10238-x
BibTeX
@article{mecfsatlas-hirsch-2025-comparison-genome,
author = {Hirsch, Annemarie G and Justice, Anne E and Poissant, Amy and Nordberg, Cara M and Josyula, Navya S and Aucott, John and Rebman, Alison W and Schwartz, Brian S},
title = {A comparison of genome-wide association analyses of persistent symptoms after Lyme disease, fibromyalgia, and myalgic encephalomyelitis - chronic fatigue syndrome.},
journal = {BMC infectious diseases},
year = {2025},
doi = {10.1186/s12879-024-10238-x},
note = {PubMed: 39994562},
url = {https://www.mecfsatlas.com/evidence/hirsch-2025-comparison-genome},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/hirsch-2025-comparison-genome
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