Nature Communications (Jun 2018)
DNA methylation as a mediator of HLA-DRB1*15:01 and a protective variant in multiple sclerosis
- Lara Kular,
- Yun Liu,
- Sabrina Ruhrmann,
- Galina Zheleznyakova,
- Francesco Marabita,
- David Gomez-Cabrero,
- Tojo James,
- Ewoud Ewing,
- Magdalena Lindén,
- Bartosz Górnikiewicz,
- Shahin Aeinehband,
- Pernilla Stridh,
- Jenny Link,
- Till F. M. Andlauer,
- Christiane Gasperi,
- Heinz Wiendl,
- Frauke Zipp,
- Ralf Gold,
- Björn Tackenberg,
- Frank Weber,
- Bernhard Hemmer,
- Konstantin Strauch,
- Stefanie Heilmann-Heimbach,
- Rajesh Rawal,
- Ulf Schminke,
- Carsten O. Schmidt,
- Tim Kacprowski,
- Andre Franke,
- Matthias Laudes,
- Alexander T. Dilthey,
- Elisabeth G. Celius,
- Helle B. Søndergaard,
- Jesper Tegnér,
- Hanne F. Harbo,
- Annette B. Oturai,
- Sigurgeir Olafsson,
- Hannes P. Eggertsson,
- Bjarni V. Halldorsson,
- Haukur Hjaltason,
- Elias Olafsson,
- Ingileif Jonsdottir,
- Kari Stefansson,
- Tomas Olsson,
- Fredrik Piehl,
- Tomas J. Ekström,
- Ingrid Kockum,
- Andrew P. Feinberg,
- Maja Jagodic
Affiliations
- Lara Kular
- Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet
- Yun Liu
- Center for Epigenetics, and Departments of Medicine, Biomedical Engineering and Mental Health, Johns Hopkins University
- Sabrina Ruhrmann
- Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet
- Galina Zheleznyakova
- Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet
- Francesco Marabita
- Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet
- David Gomez-Cabrero
- Unit of Computational Medicine, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet
- Tojo James
- Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet
- Ewoud Ewing
- Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet
- Magdalena Lindén
- Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet
- Bartosz Górnikiewicz
- Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet
- Shahin Aeinehband
- Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet
- Pernilla Stridh
- Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet
- Jenny Link
- Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet
- Till F. M. Andlauer
- Max Planck Institute of Psychiatry
- Christiane Gasperi
- Department of Neurology, Klinikum rechts der Isar, School of Medicine, Technische Universität München
- Heinz Wiendl
- German Competence Network Multiple Sclerosis (KKNMS), Klinikum Rechts der Isar, Technische Universität München
- Frauke Zipp
- German Competence Network Multiple Sclerosis (KKNMS), Klinikum Rechts der Isar, Technische Universität München
- Ralf Gold
- German Competence Network Multiple Sclerosis (KKNMS), Klinikum Rechts der Isar, Technische Universität München
- Björn Tackenberg
- German Competence Network Multiple Sclerosis (KKNMS), Klinikum Rechts der Isar, Technische Universität München
- Frank Weber
- Max Planck Institute of Psychiatry
- Bernhard Hemmer
- Department of Neurology, Klinikum rechts der Isar, School of Medicine, Technische Universität München
- Konstantin Strauch
- Institute of Genetic Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany and Institute of Medical Informatics, Biometry, and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität
- Stefanie Heilmann-Heimbach
- Institute of Human Genetics, University Hospital Bonn and Division of Genomics, Life & Brain Research Centre, University of Bonn School of Medicine
- Rajesh Rawal
- Institute of Epidemiology and Social Medicine, University of Münster
- Ulf Schminke
- Department of Neurology, University Medicine Greifswald
- Carsten O. Schmidt
- Institute for Community Medicine, University Medicine Greifswald
- Tim Kacprowski
- Interfaculty Institute for Genetics and Functional Genomics, Ernst Moritz Arndt University and University Medicine Greifswald
- Andre Franke
- Institute of Clinical Molecular Biology, Kiel University
- Matthias Laudes
- Department I of Internal Medicine, Kiel University
- Alexander T. Dilthey
- Wellcome Trust Centre for Human Genetics, University of Oxford
- Elisabeth G. Celius
- Department of Neurology, Oslo University Hospital
- Helle B. Søndergaard
- Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen
- Jesper Tegnér
- Unit of Computational Medicine, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet
- Hanne F. Harbo
- Department of Neurology, Oslo University Hospital
- Annette B. Oturai
- Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen
- Sigurgeir Olafsson
- deCODE genetics/Amgen Inc
- Hannes P. Eggertsson
- deCODE genetics/Amgen Inc
- Bjarni V. Halldorsson
- deCODE genetics/Amgen Inc
- Haukur Hjaltason
- Department of Neurology, Landspitali, The National University of Iceland
- Elias Olafsson
- Department of Neurology, Landspitali, The National University of Iceland
- Ingileif Jonsdottir
- deCODE genetics/Amgen Inc
- Kari Stefansson
- deCODE genetics/Amgen Inc
- Tomas Olsson
- Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet
- Fredrik Piehl
- Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet
- Tomas J. Ekström
- Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet
- Ingrid Kockum
- Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet
- Andrew P. Feinberg
- Center for Epigenetics, and Departments of Medicine, Biomedical Engineering and Mental Health, Johns Hopkins University
- Maja Jagodic
- Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet
- DOI
- https://doi.org/10.1038/s41467-018-04732-5
- Journal volume & issue
-
Vol. 9,
no. 1
pp. 1 – 15
Abstract
The human leukocyte antigen (HLA) haplotype DRB1*15:01 is the major risk factor for multiple sclerosis (MS). Here the authors find that DNA methylation at HLA-DRB1 gene mediates the effect of DRB1*15:01 and of a protective HLA variant on HLA-DRB1 expression and the risk of MS.
