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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

Nature Genetics volume 45, pages 1353–1360 (2013)Cite this article

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Abstract

Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10−4). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10−8), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.

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Figure 1: Discovery phase results.
Figure 2: Bayesian fine mapping within primary regions of association.

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Acknowledgements

We thank the participants, the referring nurses, the physicians and the funders. Funding was provided by the US National Institutes of Health, the Wellcome Trust, the UK MS Society, the UK Medical Research Council, the US National MS Society, the Cambridge National Institute for Health Research (NIHR) Biomedical Research Centre, DeNDRon, the Bibbi and Niels Jensens Foundation, the Swedish Brain Foundation, the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the Swedish Heart-Lung Foundation, the Foundation for Strategic Research, the Stockholm County Council, Karolinska Institutet, INSERM, Fondation d'Aide pour la Recherche sur la Sclérose en Plaques, Association Française contre les Myopathies, Infrastrutures en Biologie Santé et Agronomie (GIS-IBISA), the German Ministry for Education and Research, the German Competence Network MS, Deutsche Forschungsgemeinschaft, Munich Biotec Cluster M4, the Fidelity Biosciences Research Initiative, Research Foundation Flanders, Research Fund KU Leuven, the Belgian Charcot Foundation, Gemeinnützige Hertie Stiftung, University Zurich, the Danish MS Society, the Danish Council for Strategic Research, the Academy of Finland, the Sigrid Juselius Foundation, Helsinki University, the Italian MS Foundation, Fondazione Cariplo, the Italian Ministry of University and Research, the Torino Savings Bank Foundation, the Italian Ministry of Health, the Italian Institute of Experimental Neurology, the MS Association of Oslo, the Norwegian Research Council, the South-Eastern Norwegian Health Authorities, the Australian National Health and Medical Research Council, the Dutch MS Foundation and Kaiser Permanente. We acknowledge the British 1958 Birth Cohort, the UK National Blood Service, Vanderbilt University Medical Center's BioVU DNA Resources Core, Centre de Ressources Biologiques du Réseau Français d'Etude Génétique de la Sclérose en Plaques, the Norwegian Bone Marrow Registry, the Norwegian MS Registry and Biobank, the North American Research Committee on MS Registry, the Brigham and Women's Hospital PhenoGenetic Project and DILGOM, funded by the Academy of Finland. See the Supplementary Note for details.

Author information

Author notes

  1. Ashley H Beecham, Nikolaos A Patsopoulos, David Hafler, Philip De Jager, Stephen J Sawcer and Jacob L McCauley: These authors contributed equally to this work.

  2. Philip De Jager, Stephen J Sawcer and Jacob L McCauley: These authors jointly directed this work.

Authors and Affiliations

  1. John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida, USA

    Ashley H Beecham, Athena Hadjixenofontos, Ioanna Konidari, Clara P Manrique, Margaret A Pericak-Vance & Jacob L McCauley

  2. Department of Neurology, Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Brigham & Women's Hospital, Boston, Massachusetts, USA

    Nikolaos A Patsopoulos, Irene Y Frohlich, Michelle H Lee & Philip De Jager

  3. Department of Psychiatry, Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Brigham & Women's Hospital, Boston, Massachusetts, USA

    Nikolaos A Patsopoulos

  4. Department of Medicine, Division of Genetics, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Nikolaos A Patsopoulos

  5. Harvard Medical School, Boston, Massachusetts, USA

    Nikolaos A Patsopoulos & Philip De Jager

  6. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA

    Nikolaos A Patsopoulos

  7. The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK

    Dionysia K Xifara, Chris Spencer, Gavin Band, Céline Bellenguez, Alexander T Dilthey, Peter Donnelly, Colin Freeman, Loukas Moutsianas, Matti Pirinen, Amy Strange & Gil McVean

  8. Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA

    Mary F Davis, Nathalie C Schnetz-Boutaud & Jonathan L Haines

  9. Department of Clinical Neurosciences, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK

    Anu Kemppinen, Maria Ban, Amie Baker, Barnaby Fiddes, Alastair Compston & Stephen J Sawcer

  10. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA

    Chris Cotsapas, Cristin McCabe, David Hafler & Philip De Jager

  11. Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, USA

    Chris Cotsapas & David Hafler

  12. Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA

    Chris Cotsapas

  13. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

    Tejas S Shah, Carl Anderson, Robert Andrews, Jeffrey Barrett, Hannah Blackburn, Panos Deloukas, Sarah Edkins, Sarah E Hunt & Cordelia Langford

  14. Westmead Millennium Institute, University of Sydney, Westmead, New South Wales, Australia

    David Booth, Steve Vucic & Graeme Stewart

  15. Section of Experimental Neurology, Laboratory for Neuroimmunology, KU Leuven, Leuven, Belgium

    An Goris, Leentje Cosemans & Bénédicte Dubois

  16. Department of Neurology, Danish Multiple Sclerosis Center, Copenhagen University Hospital, Copenhagen, Denmark

    Annette Oturai, Helle Bach Søndergaard, Finn Sellebjerg & Per Soelberg Sorensen

  17. Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland

    Janna Saarela & Virpi Leppä

  18. Département de Neurologie, INSERM UMRS 975 Centre de Recherche de l'Institut du Cerveau et la Moelle Epinière (CRICM), Université Pierre et Marie Curie (UPMC), Pitié-Salpêtrière, Paris, France

    Bertrand Fontaine, Isabelle Cournu-Rebeix & Vincent Damotte

  19. Department of Neurology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany

    Bernhard Hemmer, Achim Berthele, Viola Biberacher, Dorothea Buck, Verena Grummel, Muni Hoshi, Angela Jochim, Thomas Korn, Helena Kronsbein, Rebecca C Selter & Juliane Winkelmann

  20. Munich Cluster for Systems Neurology (SyNergy), Munich, Germany

    Bernhard Hemmer & Juliane Winkelmann

  21. German Competence Network Multiple Sclerosis (KKNMS), Munich, Germany

    Bernhard Hemmer

  22. Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden

    Claes Martin

  23. Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University Medical Center, Mainz, Germany

    Frauke Zipp, Christiane Graetz, Christina M Lill, Felix Luessi, Volker Siffrin & Eva Zindler

  24. Department of Health Sciences, University of Eastern Piedmont, Novara, Italy

    Sandra D'Alfonso, Nadia Barizzone, Laura Bergamaschi & Lucia Corrado

  25. Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Novara, Italy

    Sandra D'Alfonso, Nadia Barizzone, Laura Bergamaschi & Lucia Corrado

  26. Division of Neuroscience, Laboratory of Genetics of Neurological Complex Disorders, Institute of Experimental Neurology (INSPE), San Raffaele Scientific Institute, Milan, Italy

    Filippo Martinelli-Boneschi, Paola Brambilla, Giancarlo Comi, Federica Esposito, Clara Guaschino, Giuseppe Liberatore & Melissa Sorosina

  27. Department of Neurology, Division of Neuroscience, INSPE, San Raffaele Scientific Institute, Milan, Italy

    Filippo Martinelli-Boneschi, Giancarlo Comi, Federica Esposito, Clara Guaschino, Giuseppe Liberatore, Vittorio Martinelli & Mariaemma Rodegher

  28. Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia

    Bruce Taylor

  29. Department of Neurology, Oslo University Hospital, Ullevål, Oslo, Norway

    Hanne F Harbo, Elisabeth G Celius & Inger-Lise Mero

  30. University of Oslo, Oslo, Norway

    Hanne F Harbo, Benedicte A Lie & Inger-Lise Mero

  31. Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden

    Ingrid Kockum, Jan Hillert, Tomas Olsson, Izaura L Bomfim, Lou Brundin, Maja Jagodic, Magdalena Lindén, Jenny Link, Fredrik Piehl, Emilie Sundqvist & Helga Westerlind

  32. Department of Neurology, University of California, San Francisco, Sandler Neurosciences Center, San Francisco, California, USA

    Jorge R Oksenberg, Sergio E Baranzini, Stacy J Caillier, Bruce A C Cree, Pierre-Antoine Gourraud & Stephen L Hauser

  33. Department of Neurology, Erasmus MC, Erasmus University Medical Centre, Rotterdam, The Netherlands

    Rogier Hintzen & Julia Mescheriakova

  34. Division of Epidemiology, Genetic Epidemiology and Genomics Laboratory, School of Public Health, University of California, Berkeley, Berkeley, California, USA

    Lisa F Barcellos & Hong Quach

  35. California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, California, USA

    Lisa F Barcellos

  36. Kaiser Permanente Division of Research, Oakland, California, USA

    Lisa F Barcellos, Catherine Schaefer & Ling Shen

  37. Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi Foundation Organizzazione Non Lucrativa di Utilitä Sociale (ONLUS), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Maria Nascente, Milan, Italy

    Cristina Agliardi

  38. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

    Lars Alfredsson

  39. Laboratoire d'Immunologie, Université Rennes 1, Rennes, France

    Mehdi Alizadeh

  40. Medical Research Council Biostatistics Unit, Cambridge, UK

    Luisa Bernardinelli

  41. Department of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Thomas M C Binder

  42. School of Medicine, Griffith University, Gold Coast, Queensland, Australia

    Simon Broadley

  43. Centre Hospitalier Universitaire (CHU) Pellegrin, Université Bordeaux 2, Bordeaux, France

    Bruno Brochet

  44. Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia

    Helmut Butzkueven

  45. Department of Neurology, Box Hill Hospital, Monash University, Box Hill, Victoria, Australia

    Helmut Butzkueven

  46. Service de Neurologie, Centre Hospitalier Universitaire Régional Montpellier, Montpellier, France

    William Camu

  47. Plateforme Post-Génomique P3S, Université Pierre et Marie Curie, INSERM, Paris, France

    Wassila Carpentier

  48. Department of Neuroscience, Multiple Sclerosis Center, Azienda Ospedaliera Città della Salute e della Scienza di Torino, Turin, Italy

    Paola Cavalla

  49. Department of Neuroscience, University of Turin, Turin, Italy

    Paola Cavalla

  50. Service de Neurologie, Hôpital Avicenne, Bobigny, France

    Irène Coman

  51. Department of Health Sciences, San Paolo Hospital and Filarete Foundation, University of Milan, Milan, Italy

    Daniele Cusi

  52. Service de Neurologie, CHU de Caen and INSERM U919–Groupement d'Intérêt Public Cyceron, Caen, France

    Gilles Defer

  53. Department of Neurology, Multiple Sclerosis Division, Miller School of Medicine, University of Miami, Miami, Florida, USA

    Silvia R Delgado

  54. Neurologia 2–Regional Multiple Sclerosis Centre, Azienda Ospedaliera Universitaria San Luigi, Orbassano, Turin, Italy

    Alessia di Sapio

  55. Department of Neurology, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK

    Martin Duddy

  56. Department of Neurology, University of Tampere, Medical School, Tampere, Finland

    Irina Elovaara

  57. Division of Clinical Neurology, Nottingham University Hospital, Nottingham, UK

    Nikos Evangelou

  58. Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia

    Judith Field & James S Wiley

  59. Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany

    Andre Franke

  60. Department of Pathophysiology and Transplantation, Neurology Unit, University of Milan, Milan, Italy

    Daniela Galimberti

  61. Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy

    Daniela Galimberti

  62. Kora-gen, Helmholtz Zentrum München–German Research Center for Environmental Health, Institute of Genetic Epidemiology, Neuherberg, Germany

    Christian Gieger

  63. Department of Clinical Neurology, The Ipswich Hospital National Health Service (NHS) Trust, Ipswich, UK

    Andrew Graham

  64. Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

    Hakon Hakonarson

  65. Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Hakon Hakonarson

  66. Wellcome Trust Clinical Research Facility, Southampton General Hospital, Southampton, UK

    Christopher Halfpenny

  67. Department of Neurology, Aberdeen Royal Infirmary, Aberdeen, UK

    Gillian Hall

  68. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

    Per Hall

  69. Department of Medicine at Karolinska University Hospital Solna, Atherosclerosis Research Unit, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden

    Anders Hamsten

  70. Department of Neurology, Hull Royal Infirmary, Hull, UK

    James Harley

  71. Department of Neurology, Royal Devon and Exeter Foundaton Trust Hospital, Exeter, UK

    Timothy Harrower

  72. Keele University Medical School, University Hospital of North Staffordshire, Stoke-on-Trent, UK

    Clive Hawkins

  73. UCL Genetics Institute (UGI), University College London, London, UK

    Garrett Hellenthal

  74. Department of Neurology, Poole General Hospital, Poole, UK

    Charles Hillier

  75. Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, UK

    Jeremy Hobart & John Zajicek

  76. Institute for Neuroimmunology and Clinical Multiple Sclerosis Research (inims), Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Ilijas Jelčić, Roland Martin & Mireia Sospedra

  77. Department of Neuroimmunology and Multiple Sclerosis Research, Neurology Clinic, University Hospital Zürich, Zürich, Switzerland

    Ilijas Jelčić, Roland Martin & Mireia Sospedra

  78. Department of Neurology, Division of Clinical Neurology, Leicester Royal Infirmary, Leicester, UK

    Brian Kendall

  79. Australian Neuromuscular Research Institute, University of Western Australia, Nedlands, Western Australia, Australia

    Allan Kermode

  80. Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia

    Allan Kermode

  81. Melbourne Neuroscience Institute, University of Melbourne, Melbourne, Victoria, Australia

    Trevor Kilpatrick

  82. Department of Neurology, Seinäjoki Central Hospital, Seinäjoki, Finland

    Keijo Koivisto

  83. Department of Physics, Chemistry and Biology (IFM) Bioinformatics, Linköping University, Linköping, Sweden

    Malin Larsson

  84. Fondation Jean Dausset–Centre d'Etude du Polymorphisme Humain, Paris, France

    Mark Lathrop

  85. Commissariat à l'Energie Atomique, Institut Génomique, Centre National de Génotypage, Evry, France

    Mark Lathrop

  86. McGill University and Génome Québec Innovation Centre, Montreal, Quebec, Canada

    Mark Lathrop

  87. Service de Neurologie, Hôpital Pasteur, CHRU Nice, France

    Christine Lebrun-Frenay

  88. Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia

    Jeannette Lechner-Scott

  89. Department of Neurology, Ospedale Maggiore, Novara, Italy

    Maurizio A Leone

  90. Department of Medical Genetics, Oslo University Hospital, Ullevål, Oslo, Norway

    Benedicte A Lie & Inger-Lise Mero

  91. Department of Vertebrate Genomics, Neuropsychiatric Genetics Group, Max Planck Institute for Molecular Genetics, Berlin, Germany

    Christina M Lill

  92. Department of Clinical Neurosciences and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Göteborgs Universitet, Göteborg, Sweden

    Jan Lycke

  93. Department of Psychiatry and Human Behavior, School of Medicine, University of California–Irvine, Irvine, California, USA

    Fabio Macciardi

  94. Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy

    Fabio Macciardi

  95. Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland

    Satu Männistö

  96. Canterbury District Health Board, Christchurch, New Zealand

    Deborah Mason

  97. Department of Neurology, Queen Elizabeth Medical Centre, Edgbaston, Birmingham, UK

    Gordon Mazibrada

  98. Department of Neurology, The Norwegian Multiple Sclerosis Registry and Biobank, Haukeland University Hospital, Bergen, Norway

    Kjell-Morten Myhr

  99. National Multiple Sclerosis Center Melsbroek, Melsbroek, Belgium

    Guy Nagels

  100. Neurology Department, Charing Cross Hospital, London, UK

    Richard Nicholas

  101. Department of Clinical Sciences, Lund University, Lund, Sweden

    Petra Nilsson

  102. Department of Neurology, Royal Hallamshire Hospital, Sheffield, UK

    Siân E Price

  103. Department of Neurology, University of Oulu, Oulu, Finland

    Mauri Reunanen

  104. Department of Neurology, University Hospital of Oulu, Oulu, Finland

    Mauri Reunanen

  105. Laboratory of Neurobiology, Vesalius Research Center, Leuven, Belgium

    Wim Robberecht & Vincent Thijs

  106. Experimental Neurology, Leuven Research Institute for Neurodegenerative Diseases (LIND), University of Leuven (KU Leuven), Leuven, Belgium

    Wim Robberecht & Vincent Thijs

  107. Department of Neurology, University Hospitals Leuven, Leuven, Belgium

    Wim Robberecht & Vincent Thijs

  108. Institute of Psychological Medicine and Clinical Neuroscience, Cardiff University, University Hospital of Wales, Cardiff, UK

    Neil P Robertson

  109. Department of Neurology, Greater Manchester Neurosciences Centre, Salford Royal NHS Foundation Trust, Salford, UK

    David Rog

  110. Department of Neuroscience, Centre for Experimental Neurological Therapies, Mental Health and Sensory Organs, Sapienza Università di Roma, Rome, Italy

    Marco Salvetti

  111. Department of Neurology, Royal Preston Hospital, Preston, UK

    Sandip Shaunak

  112. Department of Neurology, Norfolk and Norwich Hospital, Norwich, UK

    Simon Shields

  113. Department of Neurology, Flinders University, Adelaide, South Australia, Australia

    Mark Slee

  114. Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

    Anne Spurkland

  115. Department of Neurology, Peterborough City Hospital, Peterborough, UK

    John Thorpe

  116. Neurology and Stroke Unit, San Francesco Hospital, Nuoro, Italy

    Anna Ticca

  117. Department of Neurology, Helsinki University Central Hospital and Molecular Neurology Programme, Biomedicum, University of Helsinki, Helsinki, Finland

    Pentti Tienari

  118. Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands

    Cornelia van Duijn

  119. Division of Applied Health Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK

    Elizabeth M Visser

  120. Institute of Clinical Neurosciences, University of Bristol, Frenchay Hospital, Bristol, UK

    Alastair Wilkins

  121. Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK

    James F Wilson

  122. Institut für Humangenetik, Technische Universität München, Munich, Germany

    Juliane Winkelmann

  123. Institut für Humangenetik, Helmholtz Zentrum München–Munich, Germany

    Juliane Winkelmann

  124. Harvard NeuroDiscovery Center, Harvard Medical School, Boston, Massachusetts, USA

    Adrian J Ivinson

  125. Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA

    David Hafler

Consortia

International Multiple Sclerosis Genetics Consortium (IMSGC)

  • Ashley H Beecham
  • , Nikolaos A Patsopoulos
  • , Dionysia K Xifara
  • , Mary F Davis
  • , Anu Kemppinen
  • , Chris Cotsapas
  • , Tejas S Shah
  • , Chris Spencer
  • , David Booth
  • , An Goris
  • , Annette Oturai
  • , Janna Saarela
  • , Bertrand Fontaine
  • , Bernhard Hemmer
  • , Claes Martin
  • , Frauke Zipp
  • , Sandra D'Alfonso
  • , Filippo Martinelli-Boneschi
  • , Bruce Taylor
  • , Hanne F Harbo
  • , Ingrid Kockum
  • , Jan Hillert
  • , Tomas Olsson
  • , Maria Ban
  • , Jorge R Oksenberg
  • , Rogier Hintzen
  • , Lisa F Barcellos
  • , Wellcome Trust Case Control Consortium 2 (WTCCC2)
  • , International IBD Genetics Consortium (IIBDGC)
  • , Cristina Agliardi
  • , Lars Alfredsson
  • , Mehdi Alizadeh
  • , Carl Anderson
  • , Robert Andrews
  • , Helle Bach Søndergaard
  • , Amie Baker
  • , Gavin Band
  • , Sergio E Baranzini
  • , Nadia Barizzone
  • , Jeffrey Barrett
  • , Céline Bellenguez
  • , Laura Bergamaschi
  • , Luisa Bernardinelli
  • , Achim Berthele
  • , Viola Biberacher
  • , Thomas M C Binder
  • , Hannah Blackburn
  • , Izaura L Bomfim
  • , Paola Brambilla
  • , Simon Broadley
  • , Bruno Brochet
  • , Lou Brundin
  • , Dorothea Buck
  • , Helmut Butzkueven
  • , Stacy J Caillier
  • , William Camu
  • , Wassila Carpentier
  • , Paola Cavalla
  • , Elisabeth G Celius
  • , Irène Coman
  • , Giancarlo Comi
  • , Lucia Corrado
  • , Leentje Cosemans
  • , Isabelle Cournu-Rebeix
  • , Bruce A C Cree
  • , Daniele Cusi
  • , Vincent Damotte
  • , Gilles Defer
  • , Silvia R Delgado
  • , Panos Deloukas
  • , Alessia di Sapio
  • , Alexander T Dilthey
  • , Peter Donnelly
  • , Bénédicte Dubois
  • , Martin Duddy
  • , Sarah Edkins
  • , Irina Elovaara
  • , Federica Esposito
  • , Nikos Evangelou
  • , Barnaby Fiddes
  • , Judith Field
  • , Andre Franke
  • , Colin Freeman
  • , Irene Y Frohlich
  • , Daniela Galimberti
  • , Christian Gieger
  • , Pierre-Antoine Gourraud
  • , Christiane Graetz
  • , Andrew Graham
  • , Verena Grummel
  • , Clara Guaschino
  • , Athena Hadjixenofontos
  • , Hakon Hakonarson
  • , Christopher Halfpenny
  • , Gillian Hall
  • , Per Hall
  • , Anders Hamsten
  • , James Harley
  • , Timothy Harrower
  • , Clive Hawkins
  • , Garrett Hellenthal
  • , Charles Hillier
  • , Jeremy Hobart
  • , Muni Hoshi
  • , Sarah E Hunt
  • , Maja Jagodic
  • , Ilijas Jelčić
  • , Angela Jochim
  • , Brian Kendall
  • , Allan Kermode
  • , Trevor Kilpatrick
  • , Keijo Koivisto
  • , Ioanna Konidari
  • , Thomas Korn
  • , Helena Kronsbein
  • , Cordelia Langford
  • , Malin Larsson
  • , Mark Lathrop
  • , Christine Lebrun-Frenay
  • , Jeannette Lechner-Scott
  • , Michelle H Lee
  • , Maurizio A Leone
  • , Virpi Leppä
  • , Giuseppe Liberatore
  • , Benedicte A Lie
  • , Christina M Lill
  • , Magdalena Lindén
  • , Jenny Link
  • , Felix Luessi
  • , Jan Lycke
  • , Fabio Macciardi
  • , Satu Männistö
  • , Clara P Manrique
  • , Roland Martin
  • , Vittorio Martinelli
  • , Deborah Mason
  • , Gordon Mazibrada
  • , Cristin McCabe
  • , Inger-Lise Mero
  • , Julia Mescheriakova
  • , Loukas Moutsianas
  • , Kjell-Morten Myhr
  • , Guy Nagels
  • , Richard Nicholas
  • , Petra Nilsson
  • , Fredrik Piehl
  • , Matti Pirinen
  • , Siân E Price
  • , Hong Quach
  • , Mauri Reunanen
  • , Wim Robberecht
  • , Neil P Robertson
  • , Mariaemma Rodegher
  • , David Rog
  • , Marco Salvetti
  • , Nathalie C Schnetz-Boutaud
  • , Finn Sellebjerg
  • , Rebecca C Selter
  • , Catherine Schaefer
  • , Sandip Shaunak
  • , Ling Shen
  • , Simon Shields
  • , Volker Siffrin
  • , Mark Slee
  • , Per Soelberg Sorensen
  • , Melissa Sorosina
  • , Mireia Sospedra
  • , Anne Spurkland
  • , Amy Strange
  • , Emilie Sundqvist
  • , Vincent Thijs
  • , John Thorpe
  • , Anna Ticca
  • , Pentti Tienari
  • , Cornelia van Duijn
  • , Elizabeth M Visser
  • , Steve Vucic
  • , Helga Westerlind
  • , James S Wiley
  • , Alastair Wilkins
  • , James F Wilson
  • , Juliane Winkelmann
  • , John Zajicek
  • , Eva Zindler
  • , Jonathan L Haines
  • , Margaret A Pericak-Vance
  • , Adrian J Ivinson
  • , Graeme Stewart
  • , David Hafler
  • , Stephen L Hauser
  • , Alastair Compston
  • , Gil McVean
  • , Philip De Jager
  • , Stephen J Sawcer
  •  & Jacob L McCauley

Contributions

M.F.D., D. Booth, A.O., J.S., B. Fontaine, B.H., C. Martin, F.Z., S.D., F.M.-B., B.T., H.F.H., I. Kockum, J. Hillert, T.O., J.R.O., R.H., L.F.B., C. Agliardi, L.A., L. Bernardinelli, V.B., S.B., B.B., L. Brundin, D. Buck, H. Butzkueven, W. Camu, P.C., E.G.C., I.C., G.C., I.C.-R., B.A.C.C., G.D., S.R.D., A.d.S., B.D., M.D., I.E., F.E., N.E., J.F., A.F., I.Y.F., D.G., C. Graetz, A. Graham, C. Guaschino, C. Halfpenny, G. Hall, J. Harley, T.H., C. Hawkins, C. Hillier, J. Hobart, M.H., I.J., A.J., B.K., A. Kermode, T. Kilpatrick, K.K., T. Korn, H.K., C.L.-F., J.L.-S., M.H.L., M.A.L., G.L., B.A.L., C.M.L., F.L., J. Lycke, S.M., C.P.M., R.M., V.M., D.M., G. Mazibrada, J.M., K.-M.M., G.N., R.N., P.N., F.P., S.E.P., H.Q., M. Reunanen, W.R., N.P.R., M. Rodegher, D.R., M. Salvetti, F.S., R.C.S., C. Schaefer, S. Shaunak, L.S., S. Shields, V.S., M. Slee, P.S.S., M. Sospedra, A. Spurkland, V.T., J.T., A.T., P.T., C.v.D., E.M.V., S.V., J.S.W., A.W., J.F.W., J.Z., E.Z., J.L.H., M.A.P.-V., G.S., D.H., S.L.H., A.C., P.D.J., S.J.S. and J.L.M. were involved with case ascertainment and phenotyping. A. Kemppinen, D. Booth, A. Goris, A.O., B. Fontaine, S.D., F.M.-B., H.F.H., I. Kockum, M.B., J.R.O., L.F.B., IIBDGC, H.B.S., A. Baker, N.B., L. Bergamaschi, I.L.B., P.B., D. Buck, S.J.C., L. Corrado, L. Cosemans, I.C.-R., V.D., J.F., A.F., V.G., I.J., I. Konidari, V.L., C.M.L., M. Lindén, J. Link, C. McCabe, I.-L.M., H.Q., M. Sorosina, E.S., H.W., P.D.J., S.J.S. and J.L.M. processed the DNA. A. Kemppinen, A.O., B. Fontaine, M.B., R.H., L.F.B., WTCCC2, IIBDGC, R.A., H.B.S., N.B., T.M.C.B., H. Blackburn, P.B., W. Carpentier, L. Corrado, I.C.-R., D.C., V.D., P. Deloukas, S.E., A.F., H.H., P.H., A. Hamsten, S.E.H., I.J., I. Konidari, C.L., M. Larsson, M. Lathrop, F.M., I.-L.M., J.M., H.Q., F.S., M. Sorosina, C.v.D., J.W., D.H., P.D.J., S.J.S. and J.L.M. conducted and supervised the genotyping of samples. A.H.B., N.A.P., D.K.X., M.F.D., A. Kemppinen, C.C., T.S.S., C. Spencer, M.B., IIBDGC, C. Anderson, S.E.B., A.T.D., P. Donnelly, B. Fiddes, P.-A.G., G. Hellenthal, S.E.H., L.M., M.P., N.C.S.-B., J.L.H., M.A.P.-V., G. McVean, P.D.J., S.J.S. and J.L.M. performed the statistical analysis. A.H.B., N.A.P., D.K.X., M.F.D., A. Kemppinen, C.C., T.S.S., C. Spencer, D. Booth, A. Goris, A.O., J.S., B. Fontaine, B.H., F.Z., S.D., F.M.-B., H.F.H., I. Kockum, M.B., R.H., L.F.B., C. Agliardi, M.A., C. Anderson, R.A., H.B.S., A. Baker, G.B., N.B., J.B., C.B., L. Bernardinelli, A. Berthele, V.B., T.M.C.B., H. Blackburn, I.L.B., B.B., D. Buck, S.J.C., W. Camu, P.C., E.G.C., I.C., G.C., L. Corrado, L. Cosemans, I.C.-R., B.A.C.C., D.C., G.D., S.R.D., P. Deloukas, A.d.S., A.T.D., P. Donnelly, B.D., M.D., S.E., F.E., N.E., B. Fiddes, J.F., A.F., C.F., D.G., C. Gieger, C. Graetz, A. Graham, V.G., C. Guaschino, A. Hadjixenofontos, H.H., C. Halfpenny, P.H., G. Hall, A. Hamsten, J. Harley, T.H., C. Hawkins, G. Hellenthal, C. Hillier, J. Hobart, M.H., S.E.H., I.J., A.J., B.K., I. Konidari, H.K., C.L., M. Larsson, M. Lathrop, C.L.-F., M.A.L., V.L., G.L., B.A.L., C.M.L., F.M., C.P.M., R.M., V.M., G. Mazibrada, C. McCabe, I.-L.M., L.M., K.-M.M., R.N., M.P., S.E.P., H.Q., N.P.R., M. Rodegher, D.R., M. Salvetti, N.C.S.-B., R.C.S., C. Schaefer, S. Shaunak, L.S., S. Shields, M. Sospedra, A. Strange, J.T., A.T., E.M.V., A.W., J.F.W., J.W., J.Z., J.L.H., A.J.I., G. McVean, P.D.J., S.J.S. and J.L.M. collected and managed the project data. A.H.B., N.A.P., M.F.D., A. Kemppinen, C.C., T.S.S., C. Spencer, J.S., B.H., F.Z., S.D., F.M.-B., H.F.H., J. Hillert, T.O., M.B., J.R.O., R.H., L.F.B., L.A., C. Anderson, G.B., J.B., C.B., A. Berthele, E.G.C., G.C., P. Donnelly, F.E., C.F., C. Gieger, C. Graetz, G. Hellenthal, M.J., T. Korn, M.A.L., R.M., M.P., M. Sospedra, A. Spurkland, A. Strange, J.W., J.L.H., M.A.P.-V., A.J.I., G.S., D.H., S.L.H., A.C., G. McVean, P.D.J., S.J.S. and J.L.M. contributed to the study concept and design. A.H.B., N.A.P., D.K.X., G. McVean, P.D.J., S.J.S. and J.L.M. prepared the manuscript. All authors reviewed the final manuscript.

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Correspondence to Jacob L McCauley.

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International Multiple Sclerosis Genetics Consortium (IMSGC). Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet 45, 1353–1360 (2013). https://doi.org/10.1038/ng.2770

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