ArticleNature genetics2015
Class II HLA interactions modulate genetic risk for multiple sclerosis.
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Article in Nature genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 222 papers, 6 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
222citing papers in PubMed, 6 pooled it
23.3field-weighted citation impact, top 1% of its field
What it found
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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.
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Who cites it
222 citing papers in PubMed, 6 syntheses or guidelines pooled it, 407 citations in OpenAlex.
- Human leukocyte antigen (HLA) class I and II genetic relationships with brain imaging measures: A systematic review and meta-analysis.Brain, behavior, and immunity · 2025Pooled it
- The global prevalence of familial multiple sclerosis: an updated systematic review and meta-analysis.BMC neurology · 2021Pooled it
- Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression.Biological psychiatry · 2020Pooled it
- Pooled it
- Early complement genes are associated with visual system degeneration in multiple sclerosis.Brain : a journal of neurology · 2019Pooled it
- Smoking induces DNA methylation changes in Multiple Sclerosis patients with exposure-response relationship.Scientific reports · 2017Pooled it
- High Resolution Haplotype Analyses of Classical HLA Genes in Families With Multiple Sclerosis Highlights the Role of HLA-DP Alleles in Disease Susceptibility.Frontiers in immunology · 2021Trial
- Molecular mimicry between Anoctamin 2 and Epstein-Barr virus nuclear antigen 1 associates with multiple sclerosis risk.Proceedings of the National Academy of Sciences of the United States of America · 2019Trial
- Genetic Risk in Multiple Sclerosis: Susceptibility, Modifiers and Unresolved Questions.Neurology and therapy · 2026Review
- Multiancestry genome-wide association and multiomics analyses elucidate spatiocellular features of multiple sclerosis genetics.Nature genetics · 2026Article
- Dynamics of Myelin-Specific T-Cell Repertoires Mirror Disease Activity and Central Nervous System Trafficking in Multiple Sclerosis.International journal of molecular sciences · 2026Article
- Single cell landscape of sex differences in the different courses of multiple sclerosis.Biology of sex differences · 2026Article
- CD4Science translational medicine · 2026Article
- Shared trans-ancestry architecture of HLA-mediated disease risk in theResearch square · 2026Article
- Large-scale human genomic resources drive innovations toward forensic intelligent source attribution and precision identification.International journal of legal medicine · 2026Review
- Lifespan Modeling of Choroid Plexus Volume in Multiple Sclerosis and Its Dynamic Associations With Clinical, MRI, and HLA Susceptibility.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- Shared trans-ancestry architecture of HLA-mediated disease risk in themedRxiv : the preprint server for health sciences · 2026Article
- Immune cell-specific genetic architecture of Alzheimer's disease revealed by multi-omics analysis for therapeutic target discovery and prioritization.Translational psychiatry · 2026Article
- [Role of HLA genetic variants in autoimmune diseases].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- Review
162 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
56 authors at 20 institutions in 11 countries.
Loukas Moutsianas *Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Luke Jostins *Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Ashley H Beecham *John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida, USA.
Alexander T DiltheyWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Dionysia K XifaraWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Maria BanDepartment of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
Tejas S ShahWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
Nikolaos A PatsopoulosProgram in Translational NeuroPsychiatric Genomics, Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Lars AlfredssonInstitute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm, Sweden.
Carl A AndersonWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
Katherine E AttfieldMedical Research Council (MRC) Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Sergio E BaranziniDepartment of Neurology, University of California, San Francisco, Sandler Neurosciences Center, San Francisco, California, USA.
Jeffrey BarrettWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
Thomas M C BinderHLA Laboratory, Department of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
David BoothWestmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia.
Dorothea BuckDepartment of Neurology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
Elisabeth G CeliusDepartment of Neurology, Oslo University Hospital, Ullevål, Oslo, Norway.
Chris CotsapasProgram in Medical and Population Genetics, Broad Institute of Harvard University and MIT, Cambridge, Massachusetts, USA.
Sandra D'AlfonsoInterdisciplinary Research Center of Autoimmune Diseases (IRCAD), Department of Health Sciences, University of Eastern Piedmont, Novara, Italy.
Calliope A DendrouNuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Peter DonnellyWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Bénédicte DuboisDepartment of Neurosciences, Laboratory for Neuroimmunology, KU Leuven, Leuven, Belgium.
Bertrand FontaineINSERM, Université Pierre et Marie Curie, CNRS, Assistance Publique-Hôpitaux de Paris (AP-HP), Département des Maladies du Système Nerveux and UMRS 1127-7225, Institut Cerveau Moelle Spinal Cord and Brain Institute, Pitié-Salpêtrière, Paris, France.
Lars FuggerMedical Research Council (MRC) Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
An GorisDepartment of Neurosciences, Laboratory for Neuroimmunology, KU Leuven, Leuven, Belgium.
Pierre-Antoine GourraudDepartment of Neurology, University of California, San Francisco, Sandler Neurosciences Center, San Francisco, California, USA.
Christiane GraetzFocus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University-Medical Center, Mainz, Germany.
Bernhard HemmerDepartment of Neurology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
Jan HillertDepartment of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
International IBD Genetics Consortium (IIBDGC)
Ingrid KockumDepartment of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Stephen LeslieMurdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Melbourne, Victoria, Australia.
Christina M LillFocus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University-Medical Center, Mainz, Germany.
Filippo Martinelli-BoneschiLaboratory of Genetics of Neurological Complex Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
Jorge R OksenbergDepartment of Neurology, University of California, San Francisco, Sandler Neurosciences Center, San Francisco, California, USA.
Tomas OlssonDepartment of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Annette OturaiDepartment of Neurology, Danish Multiple Sclerosis Center, Copenhagen University Hospital, Copenhagen, Denmark.
Janna SaarelaInstitute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
Helle Bach SøndergaardDepartment of Neurology, Danish Multiple Sclerosis Center, Copenhagen University Hospital, Copenhagen, Denmark.
Anne SpurklandInstitute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Bruce TaylorMenzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia.
Juliane WinkelmannDepartment of Neurology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
Frauke ZippFocus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University-Medical Center, Mainz, Germany.
Jonathan L HainesCenter for Human Genetics Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Margaret A Pericak-VanceJohn P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida, USA.
Chris C A SpencerWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Graeme StewartWestmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia.
David A HaflerProgram in Medical and Population Genetics, Broad Institute of Harvard University and MIT, Cambridge, Massachusetts, USA.
Adrian J IvinsonHarvard NeuroDiscovery Center, Harvard Medical School, Boston, Massachusetts, USA.
Hanne F HarboDepartment of Neurology, Oslo University Hospital, Ullevål, Oslo, Norway.
Stephen L HauserDepartment of Neurology, University of California, San Francisco, Sandler Neurosciences Center, San Francisco, California, USA.
Philip L De JagerProgram in Translational NeuroPsychiatric Genomics, Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Alastair CompstonDepartment of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
Jacob L McCauleyJohn P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida, USA.
Stephen SawcerDepartment of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
Gil McVeanWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Broad Institute · USCentre for Human Genetics · GBTUM Klinikum · DEKarolinska Institutet · SEOslo University Hospital · NOThe University of Sydney · AUCopenhagen University Hospital · DKJohannes Gutenberg University Mainz · DERoyal Children's Hospital · AUUniversity of California, San Francisco · USUniversity of Cambridge · GBUniversity of Miami · USVita-Salute San Raffaele University · ITHarvard NeuroDiscovery Center · USUniversität Hamburg · DEUniversity of Helsinki · FIUniversity of Oslo · NOCenter for Human Genetics · USCentre National de la Recherche Scientifique · FRUniversità degli Studi del Piemonte Orientale “Amedeo Avogadro” · IT
Funding
VANDERBILT UNIVERSITY CTSA FOR PEDIATRIC RESEARCHUL1RR024975 · NCRR · VANDERBILT UNIVERSITY · PI BERNARD, GORDON RAPHAEL · 2007 to 2011
$45.7MA Haplotype Map for Multiple SclerosisR01NS049477 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HAUSER, STEPHEN L · 2005 to 2014
$15.3MThe Genetic Epemiology of Multiple SclerosisR01NS032830 · NINDS · VANDERBILT UNIVERSITY · PI HAINES, JONATHAN L · 1995 to 2010
$8.9MGene Expression and Regulatory Networks in Human LeukocytesRC2GM093080 · NIGMS · HARVARD MEDICAL SCHOOL · PI BENOIST, CHRISTOPHE O., MATHIS, DIANE J · 2009 to 2010
$7.3MGENE LINKAGE STUDY OF MULTIPLE SCLEROSIS SIBLING PAIRSR01NS026799 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HAUSER, STEPHEN L, OKSENBERG, JORGE R. · 1989 to 2018
$6.8MNINDS Research Education Programs for Residents and Fellows in Neurology, Neurosurgery, Neuropathology, Neuroradiology and Emergency Medicine (R25)R25NS070680 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JOSEPHSON, SCOTT ANDREW · 2010 to 2023
$6.8MThe Role of Rare Variants in Multiple Sclerosis RiskRC2NS070340 · NINDS · YALE UNIVERSITY · PI HAFLER, DAVID A. · 2009 to 2010
$1.9MExploring the consequences of the TNFRSF1A susceptibility allele for MSR01NS067305 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI DE JAGER, PHILIP L · 2009 to 2011
$1.2MMedical Research Council G0000934Medical Research Council G0700061NCRR NIH HHS 1UL1RR024975-01NCRR NIH HHS UL1 RR024975NIGMS NIH HHS RC2 GM093080NIGMS NIH HHS RC2GM093080NINDS NIH HHS NS049477NINDS NIH HHS NS26799NINDS NIH HHS R01 NS026799NINDS NIH HHS R01 NS032830NINDS NIH HHS R01NS032830NINDS NIH HHS R01 NS049477NINDS NIH HHS R01 NS067305NINDS NIH HHS R01NS067305NINDS NIH HHS R25 NS070680NINDS NIH HHS RC2 NS070340NINDS NIH HHS RC2NS070340Wellcome Trust 068545/Z/02Wellcome Trust 084702/Z/08/ZWellcome Trust 085475/B/08/ZWellcome Trust 085475/Z/08/ZWellcome Trust 098051Wellcome Trust 100956
Abstract
Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17,465 cases and 30,385 controls from 11 cohorts of European ancestry, in combination with imputation of classical HLA alleles, to build a high-resolution map of HLA genetic risk and assess the evidence for interactions involving classical HLA alleles. Among new and previously identified class II risk alleles (HLA-DRB1*15:01, HLA-DRB1*13:03, HLA-DRB1*03:01, HLA-DRB1*08:01 and HLA-DQB1*03:02) and class I protective alleles (HLA-A*02:01, HLA-B*44:02, HLA-B*38:01 and HLA-B*55:01), we find evidence for two interactions involving pairs of class II alleles: HLA-DQA1*01:01-HLA-DRB1*15:01 and HLA-DQB1*03:01-HLA-DQB1*03:02. We find no evidence for interactions between classical HLA alleles and non-HLA risk-associated variants and estimate a minimal effect of polygenic epistasis in modulating major risk alleles.
Indexed as
Genetic Predisposition to DiseaseAllelesEpistasis, GeneticHistocompatibility Antigens Class IIHumansMultiple SclerosisPolymorphism, Single NucleotideHistocompatibility Antigens Class II
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