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

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. HarboIngrid 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 Jelcic, 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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1353-1362
Number of pages10
JournalNature Genetics
Volume45
Issue number11
DOIs
Publication statusPublished - Nov 2013

ASJC Scopus subject areas

  • Genetics

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