Evidence map›Paper›PMID 30036399›Full record

ArticlePloS one2018

Identification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-associated DNA methylation patterns.

Malav S Trivedi, Elisa Oltra, Leonor Sarria, Natasha Rose, Vladimir Beljanski, Mary Ann Fletcher, Nancy G Klimas, Lubov Nathanson

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04378634 (The Influence of Epigenetic Modifications and Post-Exertional Malaise in People With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome), which is not on this map. Cited by 40 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 1 pooled it
4.7field-weighted citation impact, top 4% of its field
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.

NCT04378634 nacompletednot on this mapstarted 2021, after this paper: background citation

The Influence of Epigenetic Modifications and Post-Exertional Malaise in People With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

TypeinterventionalSponsorVrije Universiteit BrusselRan2021 to 2023Enrolled105ConditionsFatigue Syndrome, ChronicArmsExercise, Mental Stress Test
3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.

  1. Recent research in myalgic encephalomyelitis/chronic fatigue syndrome: an evidence map.Health technology assessment (Winchester, England) · 2025
    Pooled it
  2. Trial
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  16. Application of DNA Methylome Analysis to Patients with ME/CFS.Methods in molecular biology (Clifton, N.J.) · 2025
    Article
  17. Review
  18. Article
  19. Review
  20. Methylation factors as biomarkers of fibromyalgia.Annals of translational medicine · 2023
    Article
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

8 authors at 2 institutions in 2 countries.

Malav S TrivediCollege of Pharmacy, Nova Southeastern University, Fort Lauderdale, United States of America.
Elisa OltraSchool of Medicine and Dentistry, Catholic University of Valencia, Valencia, Spain.
Leonor SarriaInstitute for Neuro Immune Medicine, Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, United States of America.
Natasha RoseCollege of Pharmacy, Nova Southeastern University, Fort Lauderdale, United States of America.
Vladimir BeljanskiCell Therapy Institute, Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, United States of America.
Mary Ann FletcherInstitute for Neuro Immune Medicine, Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, United States of America.
Nancy G KlimasInstitute for Neuro Immune Medicine, Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, United States of America.
Lubov NathansonInstitute for Neuro Immune Medicine, Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, United States of America.ORCID 0000-0003-1038-9083
Nova Southeastern University · USUniversitat de València · ES

Funding

Genomic approach to find novel biomarkers and mechanisms of CFS/MER15NS087604 · NINDS · NOVA SOUTHEASTERN UNIVERSITY · PI NATHANSON, LUBOV · 2015 to 2016
$526k
Sex-specific genomic mechanisms of transcriptional regulation in ME/CFS/SEIDR21AI124187 · NIAID · NOVA SOUTHEASTERN UNIVERSITY · PI NATHANSON, LUBOV · 2016 to 2017
$347k
NIAID NIH HHS R21 AI124187NINDS NIH HHS R15 NS087604
6 · The paper itself

Abstract

backgroundMyalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex condition involving multiple organ systems and characterized by persistent/relapsing debilitating fatigue, immune dysfunction, neurological problems, and other symptoms not curable for at least 6 months. Disruption of DNA methylation patterns has been tied to various immune and neurological diseases; however, its status in ME/CFS remains uncertain. Our study aimed at identifying changes in the DNA methylation patterns that associate with ME/CFS.

methodsWe extracted genomic DNA from peripheral blood mononuclear cells from 13 ME/CFS study subjects and 12 healthy controls and measured global DNA methylation by ELISA-like method and site-specific methylation status using Illumina MethylationEPIC microarrays. Pyrosequencing validation included 33 ME/CFS cases and 31 controls from two geographically distant cohorts.

resultsGlobal DNA methylation levels of ME/CFS cases were similar to those of controls. However, microarray-based approach allowed detection of 17,296 differentially methylated CpG sites in 6,368 genes across regulatory elements and within coding regions of genes. Analysis of DNA methylation in promoter regions revealed 307 differentially methylated promoters. Ingenuity pathway analysis indicated that genes associated with differentially methylated promoters participated in at least 15 different pathways mostly related to cell signaling with a strong immune component.

conclusionsThis is the first study that has explored genome-wide epigenetic changes associated with ME/CFS using the advanced Illumina MethylationEPIC microarrays covering about 850,000 CpG sites in two geographically distant cohorts of ME/CFS cases and matched controls. Our results are aligned with previous studies that indicate a dysregulation of the immune system in ME/CFS. They also suggest a potential role of epigenetic de-regulation in the pathobiology of ME/CFS. We propose screening of larger cohorts of ME/CFS cases to determine the external validity of these epigenetic changes in order to implement them as possible diagnostic markers in clinical setting.

Indexed as

DNA MethylationCohort StudiesCpG IslandsEpigenesis, GeneticFatigue Syndrome, ChronicFemaleHumansMicroarray AnalysisMiddle AgedPromoter Regions, Genetic

Identifiers

PMID30036399
PMCPMC6056050
OpenAlexW2883484453

What OpenQuestion holds

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Registered trials

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 OpenQuestion graph.