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Nature Genetics

Publication date: 2013-01-01
Volume: 45 Pages: 1353 - 1360
Publisher: Nature Publishing Group

Author:

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

Keywords:

Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, GENOTYPE IMPUTATION, ASSOCIATION, RISK, METAANALYSIS, INFORMATION, AUTOIMMUNE, GENETICS, COMMON, RARE, TOOL, Chromosome Mapping, Gene Frequency, Genetic Loci, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Multiple Sclerosis, Polymorphism, Single Nucleotide, White People, International Multiple Sclerosis Genetics Consortium (IMSGC), Wellcome Trust Case Control Consortium 2 (WTCCC2), International IBD Genetics Consortium (IIBDGC), 06 Biological Sciences, 11 Medical and Health Sciences, Developmental Biology, 3001 Agricultural biotechnology, 3102 Bioinformatics and computational biology, 3105 Genetics

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.