Evidence map›Paper›PMID 42199389›Full record

ArticleEnvironmental epigenetics2026

DNA methylation mediates the multiple sclerosis onset risk associated with HHV-6 DNA positivity.

Alex Eisner, Steve Simpson-Yap, Daniel J Park, Ellen Morwitch, Samuel Tanner, Vicki E Maltby, Ingrid van der Mei, Jeannette Lechner-Scott, Rodney J Scott, Simon A Broadley and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

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

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

18 authors.

Alex EisnerThe Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, 3010, Australia.
Steve Simpson-YapThe Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, 3010, Australia.
Daniel J ParkMelbourne Bioinformatics, The University of Melbourne, Parkville, 3051, Australia.
Ellen MorwitchThe Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, 3010, Australia.
Samuel TannerThe Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, 3010, Australia.
Vicki E MaltbySchool of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, 2308, Australia.ORCID https://orcid.org/0000-0002-3785-4742
Ingrid van der MeiMS Research Flagship, Menzies Institute for Medical Research, University of Tasmania, Hobart, 7000, Australia.ORCID https://orcid.org/0000-0001-9009-7472
Jeannette Lechner-ScottSchool of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, 2308, Australia.
Rodney J ScottSchool of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, 2308, Australia.
Simon A BroadleySchool of Medicine and Dentistry, Gold Coast Campus, Griffith University, Southport, 4215, Australia.ORCID https://orcid.org/0000-0002-9429-4307
Rod A LeaSchool of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, 2308, Australia.
Pernilla StridhDepartment of Clinical Neuroscience, Karolinska Institutet, Stockholm, 171 77, Sweden.ORCID https://orcid.org/0000-0003-4855-0039
Tomas OlssonDepartment of Clinical Neuroscience, Karolinska Institutet, Stockholm, 171 77, Sweden.
Maja JagodicDepartment of Clinical Neuroscience, Karolinska Institutet, Stockholm, 171 77, Sweden.
Lars AlfredssonDepartment of Clinical Neuroscience, Karolinska Institutet, Stockholm, 171 77, Sweden.
Bruce V TaylorMS Research Flagship, Menzies Institute for Medical Research, University of Tasmania, Hobart, 7000, Australia.ORCID https://orcid.org/0000-0003-2807-0070
Ausimmune Investigators Group
Anne-Louise PonsonbyThe Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, 3010, Australia.ORCID https://orcid.org/0000-0002-6581-3657

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In Ausimmune, an Australian multicenter incident case-control study, Epstein-Barr virus (EBV)-related measures, including anti-EBNA antibodies and infectious mononucleosis, show multiple sclerosis (MS) associations mediated by DNA methylation (DNAm). Human herpesvirus-6 (HHV-6) DNA has also been linked to increased MS onset risk, though its mechanisms remain unknown. Therefore, we examined an expanded set of human herpesvirus indices including HHV-6 indices. We first tested associations with MS-associated DNAm modules, then assessed whether HHV-6 DNA contributes to MS onset through DNAm pathways. Serological (serum) and viral load (whole blood) measures of EBV (DNA, viral capsid antigen, early antigen diffuse and restricted), HHV-6 (DNA, IgM, IgG), cytomegalovirus (CMV) (IgG), and varicella zoster virus (DNA, IgG) were collected. DNAm was measured from whole blood (Illumina Infinium Human Methylation EPIC v1). DNAm-module (A1-A5) scores were derived using an epigenome-wide association study for MS onset risk and dimension-reduction methods. A total of 206 cases and 348 matched controls were analyzed. Multivariable linear regression demonstrated associations between HHV-6 DNA positivity and the A2-module, and between higher CMV IgG and the A4 module. Counterfactual mediation analysis indicated that 45% of the positive association of HHV-6 DNA positivity with MS onset risk was mediated through the A2 module (

Indexed as

case–controlDNA methylationhuman herpesvirus-6mediationmultiple sclerosis

Identifiers

PMID42199389
PMCPMC13199913

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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 OpenQuestion graph.