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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-11

AUTHORS

, Ashley H Beecham, Nikolaos A Patsopoulos, Dionysia K Xifara, Mary F Davis, Anu Kemppinen, Chris Cotsapas, Tejas S Shahi, 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, , , 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 Sawcer, Jacob L McCauley

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. More... »

PAGES

1353-1360

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    11

    VOLUME

    45

    Author Affiliations

  • University of Miami
  • Broad Institute
  • Wellcome Centre for Human Genetics
  • Vanderbilt University Medical Center
  • University of Cambridge
  • Yale University
  • Wellcome Sanger Institute
  • University of Sydney
  • KU Leuven
  • Bispebjerg Hospital
  • University of Helsinki
  • Sorbonne University
  • Competence Network Multiple Sclerosis
  • University Medical Center of the Johannes Gutenberg University Mainz
  • University of Eastern Piedmont Amadeo Avogadro
  • San Raffaele Hospital
  • University of Tasmania
  • University of Oslo
  • Karolinska Institute
  • University of California, San Francisco
  • Erasmus University Medical Center
  • Kaiser Permanente
  • University of Rennes 1
  • MRC Biostatistics Unit
  • University Medical Center Hamburg-Eppendorf
  • Griffith University
  • Monash University
  • University Hospital of Montpellier
  • University of Turin
  • Oslo University Hospital
  • Hôpital Avicenne
  • University of Milan
  • Cyceron
  • Royal Victoria Infirmary
  • University of Tampere
  • Queen's Medical Centre
  • Kiel University
  • Brigham and Women's Hospital
  • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
  • Helmholtz Zentrum München
  • Ipswich Hospital NHS Trust
  • University of Pennsylvania
  • Southampton General Hospital
  • Aberdeen Royal Infirmary
  • Hull Royal Infirmary
  • Royal Stoke University Hospital
  • University College London
  • Poole Hospital
  • Peninsula College of Medicine and Dentistry
  • University Hospital of Zurich
  • Leicester Royal Infirmary
  • Murdoch University
  • University of Melbourne
  • Seinäjoen Keskussairaala
  • Linköping University
  • McGill University
  • Centre Hospitalier Regional Universitaire De Dijon
  • University of Newcastle Australia
  • Azienda Ospedaliero Universitaria Maggiore della Carita
  • Max Planck Institute for Molecular Genetics
  • University of Gothenburg
  • National Institute for Health and Welfare
  • Canterbury District Health Board
  • Queen Elizabeth Hospital Birmingham
  • Harvard University
  • Haukeland University Hospital
  • Charing Cross Hospital
  • Lund University
  • Royal Hallamshire Hospital
  • University of California, Berkeley
  • Oulu University Hospital
  • Universitaire Ziekenhuizen Leuven
  • Cardiff University
  • Salford Royal NHS Foundation Trust
  • Sapienza University of Rome
  • Royal Preston Hospital
  • Norfolk and Norwich University Hospital
  • Flinders University
  • Peterborough City Hospital
  • University of Aberdeen
  • University of Edinburgh
  • Clinical Trials linked to this publication

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.2770

    DOI

    http://dx.doi.org/10.1038/ng.2770

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1035200930

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/24076602


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