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Class II HLA interactions modulate genetic risk for multiple sclerosis.
Moutsianas, Loukas; Jostins, Luke; Beecham, Ashley H; Dilthey, Alexander T; Xifara, Dionysia K; Ban, Maria; Shah, Tejas S; Patsopoulos, Nikolaos A; Alfredsson, Lars; Anderson, Carl A; Attfield, Katherine E; Baranzini, Sergio E; Barrett, Jeffrey; Binder, Thomas M C; Booth, David; Buck, Dorothea; Celius, Elisabeth G; Cotsapas, Chris; D'Alfonso, Sandra; Dendrou, Calliope A; Donnelly, Peter; Dubois, Bénédicte; Fontaine, Bertrand; Fugger, Lars; Goris, An; Gourraud, Pierre-Antoine; Graetz, Christiane; Hemmer, Bernhard; Hillert, Jan; Kockum, Ingrid; Leslie, Stephen; Lill, Christina M; Martinelli-Boneschi, Filippo; Oksenberg, Jorge R; Olsson, Tomas; Oturai, Annette; Saarela, Janna; Søndergaard, Helle Bach; Spurkland, Anne; Taylor, Bruce; Winkelmann, Juliane; Zipp, Frauke; Haines, Jonathan L; Pericak-Vance, Margaret A; Spencer, Chris C A; Stewart, Graeme; Hafler, David A; Ivinson, Adrian J; Harbo, Hanne F; Hauser, Stephen L.
Afiliación
  • Moutsianas L; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Jostins L; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Beecham AH; John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida, USA.
  • Dilthey AT; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Xifara DK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Ban M; Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
  • Shah TS; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
  • Patsopoulos NA; Program in Translational NeuroPsychiatric Genomics, Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
  • Alfredsson L; Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts, USA.
  • Anderson CA; Harvard Medical School, Boston, Massachusetts, USA.
  • Attfield KE; Program in Medical and Population Genetics, Broad Institute of Harvard University and MIT, Cambridge, Massachusetts, USA.
  • Baranzini SE; Institute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm, Sweden.
  • Barrett J; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
  • Binder TMC; Medical Research Council (MRC) Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Booth D; Department of Neurology, University of California, San Francisco, Sandler Neurosciences Center, San Francisco, California, USA.
  • Buck D; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
  • Celius EG; HLA Laboratory, Department of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Cotsapas C; Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia.
  • D'Alfonso S; Department of Neurology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
  • Dendrou CA; Department of Neurology, Oslo University Hospital, Ullevål, Oslo, Norway.
  • Donnelly P; Program in Medical and Population Genetics, Broad Institute of Harvard University and MIT, Cambridge, Massachusetts, USA.
  • Dubois B; Department of Neurology and Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
  • Fontaine B; Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.
  • Fugger L; Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Department of Health Sciences, University of Eastern Piedmont, Novara, Italy.
  • Goris A; Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Gourraud PA; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Graetz C; Department of Neurosciences, Laboratory for Neuroimmunology, KU Leuven, Leuven, Belgium.
  • Hemmer B; INSERM, 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.
  • Hillert J; Medical Research Council (MRC) Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Kockum I; Department of Neurosciences, Laboratory for Neuroimmunology, KU Leuven, Leuven, Belgium.
  • Leslie S; Department of Neurology, University of California, San Francisco, Sandler Neurosciences Center, San Francisco, California, USA.
  • Lill CM; Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University-Medical Center, Mainz, Germany.
  • Martinelli-Boneschi F; Department of Neurology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
  • Oksenberg JR; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
  • Olsson T; German Competence Network Multiple Sclerosis (KKNMS), Munich, Germany.
  • Oturai A; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
  • Søndergaard HB; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
  • Spurkland A; Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Melbourne, Victoria, Australia.
  • Taylor B; Department of Mathematics and Statistics, University of Melbourne, Parkville, Melbourne, Victoria, Australia.
  • Winkelmann J; Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University-Medical Center, Mainz, Germany.
  • Zipp F; Platform for Genome Analytics, Institutes of Neurogenetics and Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany.
  • Haines JL; Laboratory of Genetics of Neurological Complex Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
  • Pericak-Vance MA; Department of Neurology, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
  • Spencer CCA; Department of Neurology, University of California, San Francisco, Sandler Neurosciences Center, San Francisco, California, USA.
  • Stewart G; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
  • Hafler DA; Department of Neurology, Danish Multiple Sclerosis Center, Copenhagen University Hospital, Copenhagen, Denmark.
  • Ivinson AJ; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
  • Harbo HF; Department of Neurology, Danish Multiple Sclerosis Center, Copenhagen University Hospital, Copenhagen, Denmark.
  • Hauser SL; Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Nat Genet ; 47(10): 1107-1113, 2015 Oct.
Article en En | MEDLINE | ID: mdl-26343388
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*1501, HLA-DRB1*1303, HLA-DRB1*0301, HLA-DRB1*0801 and HLA-DQB1*0302) and class I protective alleles (HLA-A*0201, HLA-B*4402, HLA-B*3801 and HLA-B*5501), we find evidence for two interactions involving pairs of class II alleles HLA-DQA1*0101-HLA-DRB1*1501 and HLA-DQB1*0301-HLA-DQB1*0302. 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.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Antígenos de Histocompatibilidad Clase II / Predisposición Genética a la Enfermedad / Esclerosis Múltiple Tipo de estudio: Etiology_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2015 Tipo del documento: Article País de afiliación: Reino Unido
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Antígenos de Histocompatibilidad Clase II / Predisposición Genética a la Enfermedad / Esclerosis Múltiple Tipo de estudio: Etiology_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2015 Tipo del documento: Article País de afiliación: Reino Unido