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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Class II HLA interactions modulate genetic risk for multiple sclerosis</title><author><name sortKey="Moutsianas, Loukas" sort="Moutsianas, Loukas" uniqKey="Moutsianas L" first="Loukas" last="Moutsianas">Loukas Moutsianas</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Jostins, Luke" sort="Jostins, Luke" uniqKey="Jostins L" first="Luke" last="Jostins">Luke Jostins</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Beecham, Ashley H" sort="Beecham, Ashley H" uniqKey="Beecham A" first="Ashley H" last="Beecham">Ashley H. Beecham</name><affiliation><nlm:aff id="A2">John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida, USA.</nlm:aff></affiliation></author><author><name sortKey="Dilthey, Alexander T" sort="Dilthey, Alexander T" uniqKey="Dilthey A" first="Alexander T" last="Dilthey">Alexander T. Dilthey</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Xifara, Dionysia K" sort="Xifara, Dionysia K" uniqKey="Xifara D" first="Dionysia K" last="Xifara">Dionysia K. Xifara</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Ban, Maria" sort="Ban, Maria" uniqKey="Ban M" first="Maria" last="Ban">Maria Ban</name><affiliation><nlm:aff id="A3">Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Shah, Tejas S" sort="Shah, Tejas S" uniqKey="Shah T" first="Tejas S" last="Shah">Tejas S. Shah</name><affiliation><nlm:aff id="A4">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.</nlm:aff></affiliation></author><author><name sortKey="Patsopoulos, Nikolaos A" sort="Patsopoulos, Nikolaos A" uniqKey="Patsopoulos N" first="Nikolaos A" last="Patsopoulos">Nikolaos A. Patsopoulos</name><affiliation><nlm:aff id="A5">Program in Translational NeuroPsychiatric Genomics, Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s Hospital, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Department of Medicine, Division of Genetics, Brigham and Women’s Hospital, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A8">Program in Medical and Population Genetics, Broad Institute of Harvard University and MIT, Cambridge, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Alfredsson, Lars" sort="Alfredsson, Lars" uniqKey="Alfredsson L" first="Lars" last="Alfredsson">Lars Alfredsson</name><affiliation><nlm:aff id="A9">Institute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Anderson, Carl A" sort="Anderson, Carl A" uniqKey="Anderson C" first="Carl A" last="Anderson">Carl A. Anderson</name><affiliation><nlm:aff id="A4">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.</nlm:aff></affiliation></author><author><name sortKey="Attfield, Katherine E" sort="Attfield, Katherine E" uniqKey="Attfield K" first="Katherine E" last="Attfield">Katherine E. Attfield</name><affiliation><nlm:aff id="A10">Medical Research Council (MRC) Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Baranzini, Sergio E" sort="Baranzini, Sergio E" uniqKey="Baranzini S" first="Sergio E" last="Baranzini">Sergio E. Baranzini</name><affiliation><nlm:aff id="A11">Department of Neurology, University of California, San Francisco, Sandler Neurosciences Center, San Francisco, California, USA.</nlm:aff></affiliation></author><author><name sortKey="Barrett, Jeffrey" sort="Barrett, Jeffrey" uniqKey="Barrett J" first="Jeffrey" last="Barrett">Jeffrey Barrett</name><affiliation><nlm:aff id="A4">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.</nlm:aff></affiliation></author><author><name sortKey="Binder, Thomas M C" sort="Binder, Thomas M C" uniqKey="Binder T" first="Thomas M C" last="Binder">Thomas M C. Binder</name><affiliation><nlm:aff id="A12">HLA Laboratory, Department of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.</nlm:aff></affiliation></author><author><name sortKey="Booth, David" sort="Booth, David" uniqKey="Booth D" first="David" last="Booth">David Booth</name><affiliation><nlm:aff id="A13">Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia.</nlm:aff></affiliation></author><author><name sortKey="Buck, Dorothea" sort="Buck, Dorothea" uniqKey="Buck D" first="Dorothea" last="Buck">Dorothea Buck</name><affiliation><nlm:aff id="A14">Department of Neurology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.</nlm:aff></affiliation></author><author><name sortKey="Celius, Elisabeth G" sort="Celius, Elisabeth G" uniqKey="Celius E" first="Elisabeth G" last="Celius">Elisabeth G. Celius</name><affiliation><nlm:aff id="A15">Department of Neurology, Oslo University Hospital, Ullevål, Oslo, Norway.</nlm:aff></affiliation></author><author><name sortKey="Cotsapas, Chris" sort="Cotsapas, Chris" uniqKey="Cotsapas C" first="Chris" last="Cotsapas">Chris Cotsapas</name><affiliation><nlm:aff id="A8">Program in Medical and Population Genetics, Broad Institute of Harvard University and MIT, Cambridge, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A16">Department of Neurology and Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A17">Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.</nlm:aff></affiliation></author><author><name sortKey="D Lfonso, Sandra" sort="D Lfonso, Sandra" uniqKey="D Lfonso S" first="Sandra" last="D Lfonso">Sandra D Lfonso</name><affiliation><nlm:aff id="A18">Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Department of Health Sciences, University of Eastern Piedmont, Novara, Italy.</nlm:aff></affiliation></author><author><name sortKey="Dendrou, Calliope A" sort="Dendrou, Calliope A" uniqKey="Dendrou C" first="Calliope A" last="Dendrou">Calliope A. Dendrou</name><affiliation><nlm:aff id="A19">Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Donnelly, Peter" sort="Donnelly, Peter" uniqKey="Donnelly P" first="Peter" last="Donnelly">Peter Donnelly</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Dubois, Benedicte" sort="Dubois, Benedicte" uniqKey="Dubois B" first="Bénédicte" last="Dubois">Bénédicte Dubois</name><affiliation><nlm:aff id="A20">Department of Neurosciences, Laboratory for Neuroimmunology, KU Leuven, Leuven, Belgium.</nlm:aff></affiliation></author><author><name sortKey="Fontaine, Bertrand" sort="Fontaine, Bertrand" uniqKey="Fontaine B" first="Bertrand" last="Fontaine">Bertrand Fontaine</name><affiliation><nlm:aff id="A21">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.</nlm:aff></affiliation></author><author><name sortKey="Fugger, Lars" sort="Fugger, Lars" uniqKey="Fugger L" first="Lars" last="Fugger">Lars Fugger</name><affiliation><nlm:aff id="A10">Medical Research Council (MRC) Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A19">Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Goris, An" sort="Goris, An" uniqKey="Goris A" first="An" last="Goris">An Goris</name><affiliation><nlm:aff id="A20">Department of Neurosciences, Laboratory for Neuroimmunology, KU Leuven, Leuven, Belgium.</nlm:aff></affiliation></author><author><name sortKey="Gourraud, Pierre Antoine" sort="Gourraud, Pierre Antoine" uniqKey="Gourraud P" first="Pierre-Antoine" last="Gourraud">Pierre-Antoine Gourraud</name><affiliation><nlm:aff id="A11">Department of Neurology, University of California, San Francisco, Sandler Neurosciences Center, San Francisco, California, USA.</nlm:aff></affiliation></author><author><name sortKey="Graetz, Christiane" sort="Graetz, Christiane" uniqKey="Graetz C" first="Christiane" last="Graetz">Christiane Graetz</name><affiliation><nlm:aff id="A22">Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University–Medical Center, Mainz, Germany.</nlm:aff></affiliation></author><author><name sortKey="Hemmer, Bernhard" sort="Hemmer, Bernhard" uniqKey="Hemmer B" first="Bernhard" last="Hemmer">Bernhard Hemmer</name><affiliation><nlm:aff id="A14">Department of Neurology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.</nlm:aff></affiliation><affiliation><nlm:aff id="A23">Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.</nlm:aff></affiliation><affiliation><nlm:aff id="A24">German Competence Network Multiple Sclerosis (KKNMS), Munich, Germany.</nlm:aff></affiliation></author><author><name sortKey="Hillert, Jan" sort="Hillert, Jan" uniqKey="Hillert J" first="Jan" last="Hillert">Jan Hillert</name><affiliation><nlm:aff id="A25">Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Kockum, Ingrid" sort="Kockum, Ingrid" uniqKey="Kockum I" first="Ingrid" last="Kockum">Ingrid Kockum</name><affiliation><nlm:aff id="A25">Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Leslie, Stephen" sort="Leslie, Stephen" uniqKey="Leslie S" first="Stephen" last="Leslie">Stephen Leslie</name><affiliation><nlm:aff id="A27">Murdoch Childrens Research Institute, Royal Children’s Hospital, Parkville, Melbourne, Victoria, Australia.</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Department of Mathematics and Statistics, University of Melbourne, Parkville, Melbourne, Victoria, Australia.</nlm:aff></affiliation></author><author><name sortKey="Lill, Christina M" sort="Lill, Christina M" uniqKey="Lill C" first="Christina M" last="Lill">Christina M. Lill</name><affiliation><nlm:aff id="A22">Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University–Medical Center, Mainz, Germany.</nlm:aff></affiliation><affiliation><nlm:aff id="A29">Platform for Genome Analytics, Institutes of Neurogenetics and Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany.</nlm:aff></affiliation></author><author><name sortKey="Martinelli Boneschi, Filippo" sort="Martinelli Boneschi, Filippo" uniqKey="Martinelli Boneschi F" first="Filippo" last="Martinelli-Boneschi">Filippo Martinelli-Boneschi</name><affiliation><nlm:aff id="A30">Laboratory of Genetics of Neurological Complex Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.</nlm:aff></affiliation><affiliation><nlm:aff id="A31">Department of Neurology, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.</nlm:aff></affiliation></author><author><name sortKey="Oksenberg, Jorge R" sort="Oksenberg, Jorge R" uniqKey="Oksenberg J" first="Jorge R" last="Oksenberg">Jorge R. Oksenberg</name><affiliation><nlm:aff id="A11">Department of Neurology, University of California, San Francisco, Sandler Neurosciences Center, San Francisco, California, USA.</nlm:aff></affiliation></author><author><name sortKey="Olsson, Tomas" sort="Olsson, Tomas" uniqKey="Olsson T" first="Tomas" last="Olsson">Tomas Olsson</name><affiliation><nlm:aff id="A25">Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Oturai, Annette" sort="Oturai, Annette" uniqKey="Oturai A" first="Annette" last="Oturai">Annette Oturai</name><affiliation><nlm:aff id="A32">Department of Neurology, Danish Multiple Sclerosis Center, Copenhagen University Hospital, Copenhagen, Denmark.</nlm:aff></affiliation></author><author><name sortKey="Saarela, Janna" sort="Saarela, Janna" uniqKey="Saarela J" first="Janna" last="Saarela">Janna Saarela</name><affiliation><nlm:aff id="A33">Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.</nlm:aff></affiliation></author><author><name sortKey="S Ndergaard, Helle Bach" sort="S Ndergaard, Helle Bach" uniqKey="S Ndergaard H" first="Helle Bach" last="S Ndergaard">Helle Bach S Ndergaard</name><affiliation><nlm:aff id="A32">Department of Neurology, Danish Multiple Sclerosis Center, Copenhagen University Hospital, Copenhagen, Denmark.</nlm:aff></affiliation></author><author><name sortKey="Spurkland, Anne" sort="Spurkland, Anne" uniqKey="Spurkland A" first="Anne" last="Spurkland">Anne Spurkland</name><affiliation><nlm:aff id="A34">Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.</nlm:aff></affiliation></author><author><name sortKey="Taylor, Bruce" sort="Taylor, Bruce" uniqKey="Taylor B" first="Bruce" last="Taylor">Bruce Taylor</name><affiliation><nlm:aff id="A35">Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia.</nlm:aff></affiliation></author><author><name sortKey="Winkelmann, Juliane" sort="Winkelmann, Juliane" uniqKey="Winkelmann J" first="Juliane" last="Winkelmann">Juliane Winkelmann</name><affiliation><nlm:aff id="A14">Department of Neurology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.</nlm:aff></affiliation><affiliation><nlm:aff id="A23">Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.</nlm:aff></affiliation><affiliation><nlm:aff id="A36">Institut für Humangenetik, Technische Universität München, Munich, Germany.</nlm:aff></affiliation><affiliation><nlm:aff id="A37">Institut für Humangenetik, Helmholtz Zentrum München, Munich, Germany.</nlm:aff></affiliation><affiliation><nlm:aff id="A38">Department of Neurology and Neurological Sciences, Center for Sleep Sciences and Medicine, Stanford University, Stanford, California, USA.</nlm:aff></affiliation></author><author><name sortKey="Zipp, Frauke" sort="Zipp, Frauke" uniqKey="Zipp F" first="Frauke" last="Zipp">Frauke Zipp</name><affiliation><nlm:aff id="A22">Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University–Medical Center, Mainz, Germany.</nlm:aff></affiliation></author><author><name sortKey="Haines, Jonathan L" sort="Haines, Jonathan L" uniqKey="Haines J" first="Jonathan L" last="Haines">Jonathan L. Haines</name><affiliation><nlm:aff id="A39">Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA.</nlm:aff></affiliation></author><author><name sortKey="Pericak Vance, Margaret A" sort="Pericak Vance, Margaret A" uniqKey="Pericak Vance M" first="Margaret A" last="Pericak-Vance">Margaret A. Pericak-Vance</name><affiliation><nlm:aff id="A2">John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida, USA.</nlm:aff></affiliation></author><author><name sortKey="Spencer, Chris C A" sort="Spencer, Chris C A" uniqKey="Spencer C" first="Chris C A" last="Spencer">Chris C A. Spencer</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Stewart, Graeme" sort="Stewart, Graeme" uniqKey="Stewart G" first="Graeme" last="Stewart">Graeme Stewart</name><affiliation><nlm:aff id="A13">Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia.</nlm:aff></affiliation></author><author><name sortKey="Hafler, David A" sort="Hafler, David A" uniqKey="Hafler D" first="David A" last="Hafler">David A. Hafler</name><affiliation><nlm:aff id="A8">Program in Medical and Population Genetics, Broad Institute of Harvard University and MIT, Cambridge, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A16">Department of Neurology and Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A40">Broad Institute of Harvard University and MIT, Cambridge, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Ivinson, Adrian J" sort="Ivinson, Adrian J" uniqKey="Ivinson A" first="Adrian J" last="Ivinson">Adrian J. Ivinson</name><affiliation><nlm:aff id="A41">Harvard NeuroDiscovery Center, Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Harbo, Hanne F" sort="Harbo, Hanne F" uniqKey="Harbo H" first="Hanne F" last="Harbo">Hanne F. Harbo</name><affiliation><nlm:aff id="A15">Department of Neurology, Oslo University Hospital, Ullevål, Oslo, Norway.</nlm:aff></affiliation><affiliation><nlm:aff id="A42">University of Oslo, Oslo, Norway.</nlm:aff></affiliation></author><author><name sortKey="Hauser, Stephen L" sort="Hauser, Stephen L" uniqKey="Hauser S" first="Stephen L" last="Hauser">Stephen L. Hauser</name><affiliation><nlm:aff id="A11">Department of Neurology, University of California, San Francisco, Sandler Neurosciences Center, San Francisco, California, USA.</nlm:aff></affiliation></author><author><name sortKey="De Jager, Philip L" sort="De Jager, Philip L" uniqKey="De Jager P" first="Philip L" last="De Jager">Philip L. De Jager</name><affiliation><nlm:aff id="A5">Program in Translational NeuroPsychiatric Genomics, Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s Hospital, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Department of Medicine, Division of Genetics, Brigham and Women’s Hospital, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A8">Program in Medical and Population Genetics, Broad Institute of Harvard University and MIT, Cambridge, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Compston, Alastair" sort="Compston, Alastair" uniqKey="Compston A" first="Alastair" last="Compston">Alastair Compston</name><affiliation><nlm:aff id="A3">Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Mccauley, Jacob L" sort="Mccauley, Jacob L" uniqKey="Mccauley J" first="Jacob L" last="Mccauley">Jacob L. Mccauley</name><affiliation><nlm:aff id="A2">John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida, USA.</nlm:aff></affiliation></author><author><name sortKey="Sawcer, Stephen" sort="Sawcer, Stephen" uniqKey="Sawcer S" first="Stephen" last="Sawcer">Stephen Sawcer</name><affiliation><nlm:aff id="A3">Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Mcvean, Gil" sort="Mcvean, Gil" uniqKey="Mcvean G" first="Gil" last="Mcvean">Gil Mcvean</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26343388</idno><idno type="pmc">4874245</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874245</idno><idno type="RBID">PMC:4874245</idno><idno type="doi">10.1038/ng.3395</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">002150</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002150</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Class II HLA interactions modulate genetic risk for multiple sclerosis</title><author><name sortKey="Moutsianas, Loukas" sort="Moutsianas, Loukas" uniqKey="Moutsianas L" first="Loukas" last="Moutsianas">Loukas Moutsianas</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Jostins, Luke" sort="Jostins, Luke" uniqKey="Jostins L" first="Luke" last="Jostins">Luke Jostins</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Beecham, Ashley H" sort="Beecham, Ashley H" uniqKey="Beecham A" first="Ashley H" last="Beecham">Ashley H. Beecham</name><affiliation><nlm:aff id="A2">John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida, USA.</nlm:aff></affiliation></author><author><name sortKey="Dilthey, Alexander T" sort="Dilthey, Alexander T" uniqKey="Dilthey A" first="Alexander T" last="Dilthey">Alexander T. Dilthey</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Xifara, Dionysia K" sort="Xifara, Dionysia K" uniqKey="Xifara D" first="Dionysia K" last="Xifara">Dionysia K. Xifara</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Ban, Maria" sort="Ban, Maria" uniqKey="Ban M" first="Maria" last="Ban">Maria Ban</name><affiliation><nlm:aff id="A3">Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Shah, Tejas S" sort="Shah, Tejas S" uniqKey="Shah T" first="Tejas S" last="Shah">Tejas S. Shah</name><affiliation><nlm:aff id="A4">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.</nlm:aff></affiliation></author><author><name sortKey="Patsopoulos, Nikolaos A" sort="Patsopoulos, Nikolaos A" uniqKey="Patsopoulos N" first="Nikolaos A" last="Patsopoulos">Nikolaos A. Patsopoulos</name><affiliation><nlm:aff id="A5">Program in Translational NeuroPsychiatric Genomics, Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s Hospital, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Department of Medicine, Division of Genetics, Brigham and Women’s Hospital, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A8">Program in Medical and Population Genetics, Broad Institute of Harvard University and MIT, Cambridge, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Alfredsson, Lars" sort="Alfredsson, Lars" uniqKey="Alfredsson L" first="Lars" last="Alfredsson">Lars Alfredsson</name><affiliation><nlm:aff id="A9">Institute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Anderson, Carl A" sort="Anderson, Carl A" uniqKey="Anderson C" first="Carl A" last="Anderson">Carl A. Anderson</name><affiliation><nlm:aff id="A4">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.</nlm:aff></affiliation></author><author><name sortKey="Attfield, Katherine E" sort="Attfield, Katherine E" uniqKey="Attfield K" first="Katherine E" last="Attfield">Katherine E. Attfield</name><affiliation><nlm:aff id="A10">Medical Research Council (MRC) Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Baranzini, Sergio E" sort="Baranzini, Sergio E" uniqKey="Baranzini S" first="Sergio E" last="Baranzini">Sergio E. Baranzini</name><affiliation><nlm:aff id="A11">Department of Neurology, University of California, San Francisco, Sandler Neurosciences Center, San Francisco, California, USA.</nlm:aff></affiliation></author><author><name sortKey="Barrett, Jeffrey" sort="Barrett, Jeffrey" uniqKey="Barrett J" first="Jeffrey" last="Barrett">Jeffrey Barrett</name><affiliation><nlm:aff id="A4">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.</nlm:aff></affiliation></author><author><name sortKey="Binder, Thomas M C" sort="Binder, Thomas M C" uniqKey="Binder T" first="Thomas M C" last="Binder">Thomas M C. Binder</name><affiliation><nlm:aff id="A12">HLA Laboratory, Department of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.</nlm:aff></affiliation></author><author><name sortKey="Booth, David" sort="Booth, David" uniqKey="Booth D" first="David" last="Booth">David Booth</name><affiliation><nlm:aff id="A13">Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia.</nlm:aff></affiliation></author><author><name sortKey="Buck, Dorothea" sort="Buck, Dorothea" uniqKey="Buck D" first="Dorothea" last="Buck">Dorothea Buck</name><affiliation><nlm:aff id="A14">Department of Neurology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.</nlm:aff></affiliation></author><author><name sortKey="Celius, Elisabeth G" sort="Celius, Elisabeth G" uniqKey="Celius E" first="Elisabeth G" last="Celius">Elisabeth G. Celius</name><affiliation><nlm:aff id="A15">Department of Neurology, Oslo University Hospital, Ullevål, Oslo, Norway.</nlm:aff></affiliation></author><author><name sortKey="Cotsapas, Chris" sort="Cotsapas, Chris" uniqKey="Cotsapas C" first="Chris" last="Cotsapas">Chris Cotsapas</name><affiliation><nlm:aff id="A8">Program in Medical and Population Genetics, Broad Institute of Harvard University and MIT, Cambridge, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A16">Department of Neurology and Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A17">Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.</nlm:aff></affiliation></author><author><name sortKey="D Lfonso, Sandra" sort="D Lfonso, Sandra" uniqKey="D Lfonso S" first="Sandra" last="D Lfonso">Sandra D Lfonso</name><affiliation><nlm:aff id="A18">Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Department of Health Sciences, University of Eastern Piedmont, Novara, Italy.</nlm:aff></affiliation></author><author><name sortKey="Dendrou, Calliope A" sort="Dendrou, Calliope A" uniqKey="Dendrou C" first="Calliope A" last="Dendrou">Calliope A. Dendrou</name><affiliation><nlm:aff id="A19">Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Donnelly, Peter" sort="Donnelly, Peter" uniqKey="Donnelly P" first="Peter" last="Donnelly">Peter Donnelly</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Dubois, Benedicte" sort="Dubois, Benedicte" uniqKey="Dubois B" first="Bénédicte" last="Dubois">Bénédicte Dubois</name><affiliation><nlm:aff id="A20">Department of Neurosciences, Laboratory for Neuroimmunology, KU Leuven, Leuven, Belgium.</nlm:aff></affiliation></author><author><name sortKey="Fontaine, Bertrand" sort="Fontaine, Bertrand" uniqKey="Fontaine B" first="Bertrand" last="Fontaine">Bertrand Fontaine</name><affiliation><nlm:aff id="A21">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.</nlm:aff></affiliation></author><author><name sortKey="Fugger, Lars" sort="Fugger, Lars" uniqKey="Fugger L" first="Lars" last="Fugger">Lars Fugger</name><affiliation><nlm:aff id="A10">Medical Research Council (MRC) Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A19">Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Goris, An" sort="Goris, An" uniqKey="Goris A" first="An" last="Goris">An Goris</name><affiliation><nlm:aff id="A20">Department of Neurosciences, Laboratory for Neuroimmunology, KU Leuven, Leuven, Belgium.</nlm:aff></affiliation></author><author><name sortKey="Gourraud, Pierre Antoine" sort="Gourraud, Pierre Antoine" uniqKey="Gourraud P" first="Pierre-Antoine" last="Gourraud">Pierre-Antoine Gourraud</name><affiliation><nlm:aff id="A11">Department of Neurology, University of California, San Francisco, Sandler Neurosciences Center, San Francisco, California, USA.</nlm:aff></affiliation></author><author><name sortKey="Graetz, Christiane" sort="Graetz, Christiane" uniqKey="Graetz C" first="Christiane" last="Graetz">Christiane Graetz</name><affiliation><nlm:aff id="A22">Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University–Medical Center, Mainz, Germany.</nlm:aff></affiliation></author><author><name sortKey="Hemmer, Bernhard" sort="Hemmer, Bernhard" uniqKey="Hemmer B" first="Bernhard" last="Hemmer">Bernhard Hemmer</name><affiliation><nlm:aff id="A14">Department of Neurology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.</nlm:aff></affiliation><affiliation><nlm:aff id="A23">Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.</nlm:aff></affiliation><affiliation><nlm:aff id="A24">German Competence Network Multiple Sclerosis (KKNMS), Munich, Germany.</nlm:aff></affiliation></author><author><name sortKey="Hillert, Jan" sort="Hillert, Jan" uniqKey="Hillert J" first="Jan" last="Hillert">Jan Hillert</name><affiliation><nlm:aff id="A25">Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Kockum, Ingrid" sort="Kockum, Ingrid" uniqKey="Kockum I" first="Ingrid" last="Kockum">Ingrid Kockum</name><affiliation><nlm:aff id="A25">Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Leslie, Stephen" sort="Leslie, Stephen" uniqKey="Leslie S" first="Stephen" last="Leslie">Stephen Leslie</name><affiliation><nlm:aff id="A27">Murdoch Childrens Research Institute, Royal Children’s Hospital, Parkville, Melbourne, Victoria, Australia.</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Department of Mathematics and Statistics, University of Melbourne, Parkville, Melbourne, Victoria, Australia.</nlm:aff></affiliation></author><author><name sortKey="Lill, Christina M" sort="Lill, Christina M" uniqKey="Lill C" first="Christina M" last="Lill">Christina M. Lill</name><affiliation><nlm:aff id="A22">Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University–Medical Center, Mainz, Germany.</nlm:aff></affiliation><affiliation><nlm:aff id="A29">Platform for Genome Analytics, Institutes of Neurogenetics and Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany.</nlm:aff></affiliation></author><author><name sortKey="Martinelli Boneschi, Filippo" sort="Martinelli Boneschi, Filippo" uniqKey="Martinelli Boneschi F" first="Filippo" last="Martinelli-Boneschi">Filippo Martinelli-Boneschi</name><affiliation><nlm:aff id="A30">Laboratory of Genetics of Neurological Complex Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.</nlm:aff></affiliation><affiliation><nlm:aff id="A31">Department of Neurology, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.</nlm:aff></affiliation></author><author><name sortKey="Oksenberg, Jorge R" sort="Oksenberg, Jorge R" uniqKey="Oksenberg J" first="Jorge R" last="Oksenberg">Jorge R. Oksenberg</name><affiliation><nlm:aff id="A11">Department of Neurology, University of California, San Francisco, Sandler Neurosciences Center, San Francisco, California, USA.</nlm:aff></affiliation></author><author><name sortKey="Olsson, Tomas" sort="Olsson, Tomas" uniqKey="Olsson T" first="Tomas" last="Olsson">Tomas Olsson</name><affiliation><nlm:aff id="A25">Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Oturai, Annette" sort="Oturai, Annette" uniqKey="Oturai A" first="Annette" last="Oturai">Annette Oturai</name><affiliation><nlm:aff id="A32">Department of Neurology, Danish Multiple Sclerosis Center, Copenhagen University Hospital, Copenhagen, Denmark.</nlm:aff></affiliation></author><author><name sortKey="Saarela, Janna" sort="Saarela, Janna" uniqKey="Saarela J" first="Janna" last="Saarela">Janna Saarela</name><affiliation><nlm:aff id="A33">Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.</nlm:aff></affiliation></author><author><name sortKey="S Ndergaard, Helle Bach" sort="S Ndergaard, Helle Bach" uniqKey="S Ndergaard H" first="Helle Bach" last="S Ndergaard">Helle Bach S Ndergaard</name><affiliation><nlm:aff id="A32">Department of Neurology, Danish Multiple Sclerosis Center, Copenhagen University Hospital, Copenhagen, Denmark.</nlm:aff></affiliation></author><author><name sortKey="Spurkland, Anne" sort="Spurkland, Anne" uniqKey="Spurkland A" first="Anne" last="Spurkland">Anne Spurkland</name><affiliation><nlm:aff id="A34">Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.</nlm:aff></affiliation></author><author><name sortKey="Taylor, Bruce" sort="Taylor, Bruce" uniqKey="Taylor B" first="Bruce" last="Taylor">Bruce Taylor</name><affiliation><nlm:aff id="A35">Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia.</nlm:aff></affiliation></author><author><name sortKey="Winkelmann, Juliane" sort="Winkelmann, Juliane" uniqKey="Winkelmann J" first="Juliane" last="Winkelmann">Juliane Winkelmann</name><affiliation><nlm:aff id="A14">Department of Neurology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.</nlm:aff></affiliation><affiliation><nlm:aff id="A23">Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.</nlm:aff></affiliation><affiliation><nlm:aff id="A36">Institut für Humangenetik, Technische Universität München, Munich, Germany.</nlm:aff></affiliation><affiliation><nlm:aff id="A37">Institut für Humangenetik, Helmholtz Zentrum München, Munich, Germany.</nlm:aff></affiliation><affiliation><nlm:aff id="A38">Department of Neurology and Neurological Sciences, Center for Sleep Sciences and Medicine, Stanford University, Stanford, California, USA.</nlm:aff></affiliation></author><author><name sortKey="Zipp, Frauke" sort="Zipp, Frauke" uniqKey="Zipp F" first="Frauke" last="Zipp">Frauke Zipp</name><affiliation><nlm:aff id="A22">Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University–Medical Center, Mainz, Germany.</nlm:aff></affiliation></author><author><name sortKey="Haines, Jonathan L" sort="Haines, Jonathan L" uniqKey="Haines J" first="Jonathan L" last="Haines">Jonathan L. Haines</name><affiliation><nlm:aff id="A39">Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA.</nlm:aff></affiliation></author><author><name sortKey="Pericak Vance, Margaret A" sort="Pericak Vance, Margaret A" uniqKey="Pericak Vance M" first="Margaret A" last="Pericak-Vance">Margaret A. Pericak-Vance</name><affiliation><nlm:aff id="A2">John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida, USA.</nlm:aff></affiliation></author><author><name sortKey="Spencer, Chris C A" sort="Spencer, Chris C A" uniqKey="Spencer C" first="Chris C A" last="Spencer">Chris C A. Spencer</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Stewart, Graeme" sort="Stewart, Graeme" uniqKey="Stewart G" first="Graeme" last="Stewart">Graeme Stewart</name><affiliation><nlm:aff id="A13">Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia.</nlm:aff></affiliation></author><author><name sortKey="Hafler, David A" sort="Hafler, David A" uniqKey="Hafler D" first="David A" last="Hafler">David A. Hafler</name><affiliation><nlm:aff id="A8">Program in Medical and Population Genetics, Broad Institute of Harvard University and MIT, Cambridge, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A16">Department of Neurology and Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A40">Broad Institute of Harvard University and MIT, Cambridge, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Ivinson, Adrian J" sort="Ivinson, Adrian J" uniqKey="Ivinson A" first="Adrian J" last="Ivinson">Adrian J. Ivinson</name><affiliation><nlm:aff id="A41">Harvard NeuroDiscovery Center, Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Harbo, Hanne F" sort="Harbo, Hanne F" uniqKey="Harbo H" first="Hanne F" last="Harbo">Hanne F. Harbo</name><affiliation><nlm:aff id="A15">Department of Neurology, Oslo University Hospital, Ullevål, Oslo, Norway.</nlm:aff></affiliation><affiliation><nlm:aff id="A42">University of Oslo, Oslo, Norway.</nlm:aff></affiliation></author><author><name sortKey="Hauser, Stephen L" sort="Hauser, Stephen L" uniqKey="Hauser S" first="Stephen L" last="Hauser">Stephen L. Hauser</name><affiliation><nlm:aff id="A11">Department of Neurology, University of California, San Francisco, Sandler Neurosciences Center, San Francisco, California, USA.</nlm:aff></affiliation></author><author><name sortKey="De Jager, Philip L" sort="De Jager, Philip L" uniqKey="De Jager P" first="Philip L" last="De Jager">Philip L. De Jager</name><affiliation><nlm:aff id="A5">Program in Translational NeuroPsychiatric Genomics, Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s Hospital, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Department of Medicine, Division of Genetics, Brigham and Women’s Hospital, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A8">Program in Medical and Population Genetics, Broad Institute of Harvard University and MIT, Cambridge, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Compston, Alastair" sort="Compston, Alastair" uniqKey="Compston A" first="Alastair" last="Compston">Alastair Compston</name><affiliation><nlm:aff id="A3">Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Mccauley, Jacob L" sort="Mccauley, Jacob L" uniqKey="Mccauley J" first="Jacob L" last="Mccauley">Jacob L. Mccauley</name><affiliation><nlm:aff id="A2">John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida, USA.</nlm:aff></affiliation></author><author><name sortKey="Sawcer, Stephen" sort="Sawcer, Stephen" uniqKey="Sawcer S" first="Stephen" last="Sawcer">Stephen Sawcer</name><affiliation><nlm:aff id="A3">Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Mcvean, Gil" sort="Mcvean, Gil" uniqKey="Mcvean G" first="Gil" last="Mcvean">Gil Mcvean</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author></analytic><series><title level="j">Nature genetics</title><idno type="ISSN">1061-4036</idno><idno type="eISSN">1546-1718</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P2">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.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">9216904</journal-id><journal-id journal-id-type="pubmed-jr-id">2419</journal-id><journal-id journal-id-type="nlm-ta">Nat Genet</journal-id><journal-id journal-id-type="iso-abbrev">Nat. Genet.</journal-id><journal-title-group><journal-title>Nature genetics</journal-title></journal-title-group><issn pub-type="ppub">1061-4036</issn><issn pub-type="epub">1546-1718</issn></journal-meta><article-meta><article-id pub-id-type="pmid">26343388</article-id><article-id pub-id-type="pmc">4874245</article-id><article-id pub-id-type="doi">10.1038/ng.3395</article-id><article-id pub-id-type="manuscript">NIHMS782000</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Class II HLA interactions modulate genetic risk for multiple sclerosis</article-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Moutsianas</surname><given-names>Loukas</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Jostins</surname><given-names>Luke</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Beecham</surname><given-names>Ashley H</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Dilthey</surname><given-names>Alexander T</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Xifara</surname><given-names>Dionysia K</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Ban</surname><given-names>Maria</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Shah</surname><given-names>Tejas S</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Patsopoulos</surname><given-names>Nikolaos A</given-names></name><xref ref-type="aff" rid="A5">5</xref><xref ref-type="aff" rid="A6">6</xref><xref ref-type="aff" rid="A7">7</xref><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Alfredsson</surname><given-names>Lars</given-names></name><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Anderson</surname><given-names>Carl A</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Attfield</surname><given-names>Katherine E</given-names></name><xref ref-type="aff" rid="A10">10</xref></contrib><contrib contrib-type="author"><name><surname>Baranzini</surname><given-names>Sergio E</given-names></name><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Barrett</surname><given-names>Jeffrey</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Binder</surname><given-names>Thomas M C</given-names></name><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>Booth</surname><given-names>David</given-names></name><xref ref-type="aff" rid="A13">13</xref></contrib><contrib contrib-type="author"><name><surname>Buck</surname><given-names>Dorothea</given-names></name><xref ref-type="aff" rid="A14">14</xref></contrib><contrib contrib-type="author"><name><surname>Celius</surname><given-names>Elisabeth G</given-names></name><xref ref-type="aff" rid="A15">15</xref></contrib><contrib contrib-type="author"><name><surname>Cotsapas</surname><given-names>Chris</given-names></name><xref ref-type="aff" rid="A8">8</xref><xref ref-type="aff" rid="A16">16</xref><xref ref-type="aff" rid="A17">17</xref></contrib><contrib contrib-type="author"><name><surname>D’Alfonso</surname><given-names>Sandra</given-names></name><xref ref-type="aff" rid="A18">18</xref></contrib><contrib contrib-type="author"><name><surname>Dendrou</surname><given-names>Calliope A</given-names></name><xref ref-type="aff" rid="A19">19</xref></contrib><contrib contrib-type="author"><name><surname>Donnelly</surname><given-names>Peter</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Dubois</surname><given-names>Bénédicte</given-names></name><xref ref-type="aff" rid="A20">20</xref></contrib><contrib contrib-type="author"><name><surname>Fontaine</surname><given-names>Bertrand</given-names></name><xref ref-type="aff" rid="A21">21</xref></contrib><contrib contrib-type="author"><name><surname>Fugger</surname><given-names>Lars</given-names></name><xref ref-type="aff" rid="A10">10</xref><xref ref-type="aff" rid="A19">19</xref></contrib><contrib contrib-type="author"><name><surname>Goris</surname><given-names>An</given-names></name><xref ref-type="aff" rid="A20">20</xref></contrib><contrib contrib-type="author"><name><surname>Gourraud</surname><given-names>Pierre-Antoine</given-names></name><xref 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contrib-type="author"><name><surname>Saarela</surname><given-names>Janna</given-names></name><xref ref-type="aff" rid="A33">33</xref></contrib><contrib contrib-type="author"><name><surname>Søndergaard</surname><given-names>Helle Bach</given-names></name><xref ref-type="aff" rid="A32">32</xref></contrib><contrib contrib-type="author"><name><surname>Spurkland</surname><given-names>Anne</given-names></name><xref ref-type="aff" rid="A34">34</xref></contrib><contrib contrib-type="author"><name><surname>Taylor</surname><given-names>Bruce</given-names></name><xref ref-type="aff" rid="A35">35</xref></contrib><contrib contrib-type="author"><name><surname>Winkelmann</surname><given-names>Juliane</given-names></name><xref ref-type="aff" rid="A14">14</xref><xref ref-type="aff" rid="A23">23</xref><xref ref-type="aff" rid="A36">36</xref><xref ref-type="aff" rid="A37">37</xref><xref ref-type="aff" rid="A38">38</xref></contrib><contrib contrib-type="author"><name><surname>Zipp</surname><given-names>Frauke</given-names></name><xref ref-type="aff" rid="A22">22</xref></contrib><contrib contrib-type="author"><name><surname>Haines</surname><given-names>Jonathan L</given-names></name><xref ref-type="aff" rid="A39">39</xref></contrib><contrib contrib-type="author"><name><surname>Pericak-Vance</surname><given-names>Margaret A</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Spencer</surname><given-names>Chris C A</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Stewart</surname><given-names>Graeme</given-names></name><xref ref-type="aff" rid="A13">13</xref></contrib><contrib contrib-type="author"><name><surname>Hafler</surname><given-names>David A</given-names></name><xref ref-type="aff" rid="A8">8</xref><xref ref-type="aff" rid="A16">16</xref><xref ref-type="aff" rid="A40">40</xref></contrib><contrib contrib-type="author"><name><surname>Ivinson</surname><given-names>Adrian J</given-names></name><xref ref-type="aff" rid="A41">41</xref></contrib><contrib contrib-type="author"><name><surname>Harbo</surname><given-names>Hanne F</given-names></name><xref ref-type="aff" rid="A15">15</xref><xref ref-type="aff" rid="A42">42</xref></contrib><contrib contrib-type="author"><name><surname>Hauser</surname><given-names>Stephen L</given-names></name><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>De Jager</surname><given-names>Philip L</given-names></name><xref ref-type="aff" rid="A5">5</xref><xref ref-type="aff" rid="A6">6</xref><xref ref-type="aff" rid="A7">7</xref><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Compston</surname><given-names>Alastair</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>McCauley</surname><given-names>Jacob L</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Sawcer</surname><given-names>Stephen</given-names></name><xref ref-type="aff" rid="A3">3</xref><xref ref-type="author-notes" rid="FN1">44</xref></contrib><contrib contrib-type="author"><name><surname>McVean</surname><given-names>Gil</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="author-notes" rid="FN1">44</xref></contrib><on-behalf-of>for the International Multiple Sclerosis Genetics Consortium</on-behalf-of></contrib-group><aff id="A1"><label>1</label>Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</aff><aff id="A2"><label>2</label>John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida, USA.</aff><aff id="A3"><label>3</label>Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.</aff><aff id="A4"><label>4</label>Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.</aff><aff id="A5"><label>5</label>Program in Translational NeuroPsychiatric Genomics, Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s Hospital, Boston, Massachusetts, USA.</aff><aff id="A6"><label>6</label>Department of Medicine, Division of Genetics, Brigham and Women’s Hospital, Boston, Massachusetts, USA.</aff><aff id="A7"><label>7</label>Harvard Medical School, Boston, Massachusetts, USA.</aff><aff id="A8"><label>8</label>Program in Medical and Population Genetics, Broad Institute of Harvard University and MIT, Cambridge, Massachusetts, USA.</aff><aff id="A9"><label>9</label>Institute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm, Sweden.</aff><aff id="A10"><label>10</label>Medical Research Council (MRC) Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.</aff><aff id="A11"><label>11</label>Department of Neurology, University of California, San Francisco, Sandler Neurosciences Center, San Francisco, California, USA.</aff><aff id="A12"><label>12</label>HLA Laboratory, Department of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.</aff><aff id="A13"><label>13</label>Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia.</aff><aff id="A14"><label>14</label>Department of Neurology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.</aff><aff id="A15"><label>15</label>Department of Neurology, Oslo University Hospital, Ullevål, Oslo, Norway.</aff><aff id="A16"><label>16</label>Department of Neurology and Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.</aff><aff id="A17"><label>17</label>Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.</aff><aff id="A18"><label>18</label>Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Department of Health Sciences, University of Eastern Piedmont, Novara, Italy.</aff><aff id="A19"><label>19</label>Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.</aff><aff id="A20"><label>20</label>Department of Neurosciences, Laboratory for Neuroimmunology, KU Leuven, Leuven, Belgium.</aff><aff id="A21"><label>21</label>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.</aff><aff id="A22"><label>22</label>Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University–Medical Center, Mainz, Germany.</aff><aff id="A23"><label>23</label>Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.</aff><aff id="A24"><label>24</label>German Competence Network Multiple Sclerosis (KKNMS), Munich, Germany.</aff><aff id="A25"><label>25</label>Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.</aff><aff id="A26"><label>26</label>A full list of members and affiliations appears in the<xref ref-type="supplementary-material" rid="SD1">Supplementary Note</xref>.</aff><aff id="A27"><label>27</label>Murdoch Childrens Research Institute, Royal Children’s Hospital, Parkville, Melbourne, Victoria, Australia.</aff><aff id="A28"><label>28</label>Department of Mathematics and Statistics, University of Melbourne, Parkville, Melbourne, Victoria, Australia.</aff><aff id="A29"><label>29</label>Platform for Genome Analytics, Institutes of Neurogenetics and Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany.</aff><aff id="A30"><label>30</label>Laboratory of Genetics of Neurological Complex Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.</aff><aff id="A31"><label>31</label>Department of Neurology, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.</aff><aff id="A32"><label>32</label>Department of Neurology, Danish Multiple Sclerosis Center, Copenhagen University Hospital, Copenhagen, Denmark.</aff><aff id="A33"><label>33</label>Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.</aff><aff id="A34"><label>34</label>Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.</aff><aff id="A35"><label>35</label>Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia.</aff><aff id="A36"><label>36</label>Institut für Humangenetik, Technische Universität München, Munich, Germany.</aff><aff id="A37"><label>37</label>Institut für Humangenetik, Helmholtz Zentrum München, Munich, Germany.</aff><aff id="A38"><label>38</label>Department of Neurology and Neurological Sciences, Center for Sleep Sciences and Medicine, Stanford University, Stanford, California, USA.</aff><aff id="A39"><label>39</label>Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA.</aff><aff id="A40"><label>40</label>Broad Institute of Harvard University and MIT, Cambridge, Massachusetts, USA.</aff><aff id="A41"><label>41</label>Harvard NeuroDiscovery Center, Harvard Medical School, Boston, Massachusetts, USA.</aff><aff id="A42"><label>42</label>University of Oslo, Oslo, Norway.</aff><author-notes><corresp id="CR1">Correspondence should be addressed to G.M. (<email>mcvean@well.ox.ac.uk</email>).</corresp><fn id="FN1"><label>44</label><p id="P1">These authors jointly supervised this work.</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>28</day><month>4</month><year>2016</year></pub-date><pub-date pub-type="epub"><day>07</day><month>9</month><year>2015</year></pub-date><pub-date pub-type="ppub"><month>10</month><year>2015</year></pub-date><pub-date pub-type="pmc-release"><day>20</day><month>5</month><year>2016</year></pub-date><volume>47</volume><issue>10</issue><fpage>1107</fpage><lpage>1113</lpage><pmc-comment>elocation-id from pubmed: 10.1038/ng.3395</pmc-comment>
<permissions><license license-type="permissions-link"><license-p>Reprints and permissions information is available online at <ext-link ext-link-type="uri" xlink:href="http://www.nature.com/reprints/index.html">http://www.nature.com/reprints/index.html</ext-link>.</license-p></license></permissions><abstract><p id="P2">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.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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