Evidence map›Paper›PMID 42811334›Full record

ArticleJournal of translational medicine2026

Epigenome-wide profiling identifies distinct DNA methylation architecture underlying ME/CFS and fibromyalgia symptom burden.

Andrea Polli, Jolien Hendrix, Arne Wyns, Jente Van Campenhout, Sabine Allard, Joeri L Aerts, Thessa Laeremans, Huanyu Xiong, Yanthe Buntinx, Joni Michiels and 4 more

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Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Andrea Polli *Pain in Motion (PAIN) Research Group, Department of Physical Therapy, Human Physiology and Anatomy, Faculty of Physical Education & Physical Therapy, Vrije Universiteit Brussel, Brussels, Belgium. andrea.polli@vub.be.ORCID http://orcid.org/0000-0001-8559-2217
Jolien Hendrix *Pain in Motion (PAIN) Research Group, Department of Physical Therapy, Human Physiology and Anatomy, Faculty of Physical Education & Physical Therapy, Vrije Universiteit Brussel, Brussels, Belgium.
Arne WynsPain in Motion (PAIN) Research Group, Department of Physical Therapy, Human Physiology and Anatomy, Faculty of Physical Education & Physical Therapy, Vrije Universiteit Brussel, Brussels, Belgium.
Jente Van CampenhoutPain in Motion (PAIN) Research Group, Department of Physical Therapy, Human Physiology and Anatomy, Faculty of Physical Education & Physical Therapy, Vrije Universiteit Brussel, Brussels, Belgium.
Sabine AllardDepartment of Internal Medicine and Infectious Diseases, Universitair Ziekenhuis Brussel, Brussels, Belgium.
Joeri L AertsNeuro-Aging and Viro-Immunotherapy (NAVI) Research Group, Vrije Universiteit Brussel, Brussels, Belgium.
Thessa LaeremansNeuro-Aging and Viro-Immunotherapy (NAVI) Research Group, Vrije Universiteit Brussel, Brussels, Belgium.
Huanyu XiongPain in Motion (PAIN) Research Group, Department of Physical Therapy, Human Physiology and Anatomy, Faculty of Physical Education & Physical Therapy, Vrije Universiteit Brussel, Brussels, Belgium.
Yanthe BuntinxPain in Motion (PAIN) Research Group, Department of Physical Therapy, Human Physiology and Anatomy, Faculty of Physical Education & Physical Therapy, Vrije Universiteit Brussel, Brussels, Belgium.
Joni MichielsPain in Motion (PAIN) Research Group, Department of Physical Therapy, Human Physiology and Anatomy, Faculty of Physical Education & Physical Therapy, Vrije Universiteit Brussel, Brussels, Belgium.
Jinane Ben AmarPain in Motion (PAIN) Research Group, Department of Physical Therapy, Human Physiology and Anatomy, Faculty of Physical Education & Physical Therapy, Vrije Universiteit Brussel, Brussels, Belgium.
Lode GodderisDepartment of Public Health and Primary Care, Centre for Environment & Health, KU Leuven, Belgium.
Bernard ThienpontDepartment of Human Genetics, Laboratory for Functional Epigenetics, Herestraat 49, KU Leuven, Belgium.
Jo NijsPain in Motion (PAIN) Research Group, Department of Physical Therapy, Human Physiology and Anatomy, Faculty of Physical Education & Physical Therapy, Vrije Universiteit Brussel, Brussels, Belgium.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia are overlapping chronic disorders characterized by fatigue, pain, cognitive dysfunction, sleep disturbance, and multisystem symptoms. Whether peripheral blood DNA methylation reflects diagnostic categories, quantitative symptom burden, or both remains unclear. We aimed to identify DNA methylation axes associated with diagnosis, symptom dimensions, and clinical differences between these conditions.

methodsThis cross-sectional study included 188 women: 73 healthy controls, 71 with ME/CFS, and 44 with fibromyalgia. DNA methylation was profiled in peripheral blood mononuclear cells using the Illumina MethylationEPIC v2 array. Principal component analysis identified latent methylation axes. Linear models adjusted for age, body mass index, and estimated immune-cell composition tested associations with diagnostic group and clinical measures. Region-level methylation analyses, functional enrichment, bootstrap resampling, permutation testing, leave-one-out analyses, and medication/comorbidity sensitivity analyses were performed.

resultsBoth patient groups had greater symptom burden than healthy controls but differed clinically. Fibromyalgia showed greater widespread pain, pain catastrophizing, central sensitization inventory scores, and temporal summation, whereas ME/CFS showed greater post-exertional malaise, cognitive symptoms, and lower physical activity. Two methylation axes showed clinically relevant associations. PC5 differentiated ME/CFS from fibromyalgia and healthy controls and was associated mainly with post-exertional malaise and cognitive symptoms. PC6 separated both patient groups from healthy controls but not from each other, and was associated with broader symptom burden, including widespread pain, pain impact, sleep disturbance, visceral symptoms, and temporal summation. The temporal summation association, together with higher widespread pain and temporal summation in fibromyalgia, suggests that PC6 includes a pain-related component extending to experimentally assessed nociceptive summation. Region-level analyses identified 591 PC5-associated and 54 PC6-associated high-confidence differentially methylated regions. Enrichment implicated neuroimmune, metabolic, cytokine, NF-κB, JAK-STAT, TGF-β, and immune-regulatory pathways. Sensitivity analyses supported the stability of the main associations.

conclusionsPeripheral blood DNA methylation profiles identified partly distinct but overlapping DNA methylation axes in ME/CFS and fibromyalgia. PC5 was aligned with post-exertional malaise and cognitive symptoms, whereas PC6 was aligned with broader pain-related multisystem burden. Independent replication and longitudinal studies are needed to establish clinical utility.

Indexed as

DNA MethylationEpigenomeFatigue Syndrome, ChronicFibromyalgiaSymptom BurdenAdultCase-Control StudiesCross-Sectional StudiesFemaleHumansMiddle AgedPrincipal Component AnalysisDNA methylationEpigeneticsEpigenome-wide association studyFibromyalgiaMyalgic encephalomyelitis/chronic fatigue syndrome

Identifiers

PMID42811334
PMCPMC13625321

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.