ArticleNature communications2018
DNA methylation as a mediator of HLA-DRB1*15:01 and a protective variant in multiple sclerosis.
Open access · goldAbstract read
In one paragraph
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
119citing papers in PubMed, 2 pooled it
8.4field-weighted citation impact, top 2% of its field
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.
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.
Who cites it
119 citing papers in PubMed, 2 syntheses or guidelines pooled it, 209 citations in OpenAlex.
- Genes, Gene Loci, and Their Impacts on the Immune System in the Development of Multiple Sclerosis: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- A meta-analysis of immune-cell fractions at high resolution reveals novel associations with common phenotypes and health outcomes.Genome medicine · 2023Pooled it
- Epigenetic Insights in Pediatric Multiple Sclerosis: DNA Methylation Highlights an Involvement of Epstein-Barr Virus Infection and Host Immune Networks.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- Integrative Multi-Omics Analysis of Multiple Sclerosis Reveals Cell-Type-Specific Regulatory Landscapes and Discordant Methylation-Expression Coupling.International journal of molecular sciences · 2026Article
- Distinct Regulatory DNA Methylation Signatures Across Multiple Sclerosis, Neuromyelitis Optica, and Neurological Post-Acute Sequelae of COVID-19.Journal of clinical medicine · 2026Article
- Viral associations in multiple sclerosis: pathogenetic mechanisms and therapeutic implications.Virology journal · 2026Review
- Article
- Guidelines on optimizing DNA methylation reference panels for cell-type deconvolution.Communications biology · 2026Article
- Tailoring treatments: pharmacogenomics in the management of neurodegenerative diseases.Acta neurologica Belgica · 2026Review
- Epstein-Barr Virus, Lower Vitamin D, Low Sun Exposure, and HLA-DRB1*1501 Risk Variant Share Common Epigenetic Pathways Leading to Multiple Sclerosis Onset.Annals of neurology · 2026Article
- Mediterranean Pattern Diet in Multiple Sclerosis: A Review Focusing on Immunometabolites.Current neuropharmacology · 2026Review
- DNA methylation mediates the multiple sclerosis onset risk associated with HHV-6 DNA positivity.Environmental epigenetics · 2026Article
- Subgroups based on autoantibody status associated with clinical manifestations,Frontiers in immunology · 2026Article
- Adolescent multi-omics and Mendelian randomization reveal transdiagnostic molecular mechanisms in psychiatric disorders.Nature. Mental health · 2026Article
- Redefining multiple sclerosis therapy through microbial immunomodulation and epigenetic control.Journal of translational autoimmunity · 2025Review
- Multiple sclerosis pathophysiology: a comprehensive review of genetic, environmental, and immunological drivers.Inflammopharmacology · 2025Review
- DNA methylation and telomere length in 2-5 year olds with intrauterine preeclampsia exposure: a P4 sub-study.Clinical epigenetics · 2025Article
- Variations in Innate Immune Cell Subtypes Correlate with Epigenetic Clocks, Inflammaging and Health Outcomes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- HLA-DRB1*15:01 is associated with a reduced likelihood of longevity in northern European men.Genome medicine · 2025Article
- Differential DNA methylation and gene expression in stem cell-derived cardiomyocytes from patients with and without a history of clozapine-induced myocarditis.Journal of psychiatry & neuroscience : JPN · 2025Article
59 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
48 authors at 19 institutions in 9 countries.
Lara KularDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden.
Yun LiuCenter for Epigenetics, and Departments of Medicine, Biomedical Engineering and Mental Health, Johns Hopkins University, Baltimore, MD, 21205, USA.
Sabrina RuhrmannDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden.
Galina ZheleznyakovaDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden.
Francesco MarabitaDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden.ORCID http://orcid.org/0000-0001-6180-0106
David Gomez-CabreroUnit of Computational Medicine, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden.
Tojo JamesDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden.
Ewoud EwingDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden.ORCID http://orcid.org/0000-0001-8644-366X
Magdalena LindénDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden.
Bartosz GórnikiewiczDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden.
Shahin AeinehbandDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden.
Pernilla StridhDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden.
Jenny LinkDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-6134-9404
Till F M AndlauerMax Planck Institute of Psychiatry, 80804, Munich, Germany.ORCID http://orcid.org/0000-0002-2917-5889
Christiane GasperiDepartment of Neurology, Klinikum rechts der Isar, School of Medicine, Technische Universität München, 81675, Munich, Germany.
Heinz WiendlGerman Competence Network Multiple Sclerosis (KKNMS), Klinikum Rechts der Isar, Technische Universität München, 81675, Munich, Germany.
Frauke ZippGerman Competence Network Multiple Sclerosis (KKNMS), Klinikum Rechts der Isar, Technische Universität München, 81675, Munich, Germany.ORCID http://orcid.org/0000-0002-1231-1928
Ralf GoldGerman Competence Network Multiple Sclerosis (KKNMS), Klinikum Rechts der Isar, Technische Universität München, 81675, Munich, Germany.
Björn TackenbergGerman Competence Network Multiple Sclerosis (KKNMS), Klinikum Rechts der Isar, Technische Universität München, 81675, Munich, Germany.
Frank WeberMax Planck Institute of Psychiatry, 80804, Munich, Germany.
Bernhard HemmerDepartment of Neurology, Klinikum rechts der Isar, School of Medicine, Technische Universität München, 81675, Munich, Germany.
Konstantin StrauchInstitute of Genetic Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany and Institute of Medical Informatics, Biometry, and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, 80539, Munich, Germany.
Stefanie Heilmann-HeimbachInstitute of Human Genetics, University Hospital Bonn and Division of Genomics, Life & Brain Research Centre, University of Bonn School of Medicine, 53113, Bonn, Germany.
Rajesh RawalInstitute of Epidemiology and Social Medicine, University of Münster, 48149, Münster, Germany.
Ulf SchminkeDepartment of Neurology, University Medicine Greifswald, 17489, Greifswald, Germany.
Carsten O SchmidtInstitute for Community Medicine, University Medicine Greifswald, 17489, Greifswald, Germany.
Tim KacprowskiInterfaculty Institute for Genetics and Functional Genomics, Ernst Moritz Arndt University and University Medicine Greifswald, 17489, Greifswald, Germany.ORCID http://orcid.org/0000-0002-5393-2413
Andre FrankeInstitute of Clinical Molecular Biology, Kiel University, 24105, Kiel, Germany.ORCID http://orcid.org/0000-0003-1530-5811
Matthias LaudesDepartment I of Internal Medicine, Kiel University, 24105, Kiel, Germany.
Alexander T DiltheyWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
Elisabeth G CeliusDepartment of Neurology, Oslo University Hospital, 0372, Oslo, Norway.
Helle B SøndergaardDanish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, 2100, Copenhagen, Denmark.
Jesper TegnérUnit of Computational Medicine, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden.
Hanne F HarboDepartment of Neurology, Oslo University Hospital, 0372, Oslo, Norway.
Annette B OturaiDanish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, 2100, Copenhagen, Denmark.
Sigurgeir OlafssondeCODE genetics/Amgen Inc, 101, Reykjavik, Iceland.
Hannes P EggertssondeCODE genetics/Amgen Inc, 101, Reykjavik, Iceland.ORCID http://orcid.org/0000-0002-1674-9978
Bjarni V HalldorssondeCODE genetics/Amgen Inc, 101, Reykjavik, Iceland.ORCID http://orcid.org/0000-0003-0756-0767
Haukur HjaltasonDepartment of Neurology, Landspitali, The National University of Iceland, 101, Reykjavik, Iceland.
Elias OlafssonDepartment of Neurology, Landspitali, The National University of Iceland, 101, Reykjavik, Iceland.
Ingileif JonsdottirdeCODE genetics/Amgen Inc, 101, Reykjavik, Iceland.
Kari StefanssondeCODE genetics/Amgen Inc, 101, Reykjavik, Iceland.
Tomas OlssonDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden.
Fredrik PiehlDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden.
Tomas J EkströmDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden.
Ingrid KockumDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden.
Andrew P FeinbergCenter for Epigenetics, and Departments of Medicine, Biomedical Engineering and Mental Health, Johns Hopkins University, Baltimore, MD, 21205, USA. afeinberg@jhu.edu.ORCID http://orcid.org/0000-0002-8364-1991
Maja JagodicDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden. Maja.Jagodic@ki.se.
Karolinska Institutet · SEdeCODE Genetics (Iceland) · ISTUM Klinikum · DEChristian-Albrechts-Universität zu Kiel · DEOslo University Hospital · NOUniversitätsmedizin Greifswald · DEUniversity of Copenhagen · DKUniversity of Iceland · ISUniversity of Münster · DECentre for Human Genetics · GBHelmholtz Zentrum München · DEJohannes Gutenberg University Mainz · DEJohns Hopkins University · USMax Planck Institute of Psychiatry · DEPhilipps University of Marburg · DEReykjavík University · ISShanghai Medical College of Fudan University · CNSt. Josef-Hospital · DEUniversity of Bonn · DE
Funding
A General Stochastic Epigenetic Model for Evolution, Development, and DiseaseDP1ES022579 · NIEHS · JOHNS HOPKINS UNIVERSITY · PI FEINBERG, ANDREW P. · 2012 to 2015
$3.2MNIEHS NIH HHS DP1 ES022579
Abstract
The human leukocyte antigen (HLA) haplotype DRB1*15:01 is the major risk factor for multiple sclerosis (MS). Here, we find that DRB1*15:01 is hypomethylated and predominantly expressed in monocytes among carriers of DRB1*15:01. A differentially methylated region (DMR) encompassing HLA-DRB1 exon 2 is particularly affected and displays methylation-sensitive regulatory properties in vitro. Causal inference and Mendelian randomization provide evidence that HLA variants mediate risk for MS via changes in the HLA-DRB1 DMR that modify HLA-DRB1 expression. Meta-analysis of 14,259 cases and 171,347 controls confirms that these variants confer risk from DRB1*15:01 and also identifies a protective variant (rs9267649, p < 3.32 × 10
Indexed as
DNA MethylationPolymorphism, Single NucleotideAdultAgedCells, CulturedCohort StudiesFemaleGene Expression RegulationGenetic Predisposition to DiseaseHLA-DRB1 ChainsHumansMaleMeta-Analysis as TopicMiddle AgedMultiple SclerosisRisk FactorsHLA-DRB1*15:01 antigenHLA-DRB1 Chains
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