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

Beecham, Ashley H.; Patsopoulos, Nikolaos A.; Xifara, Dionysia K.; Davis, Mary F.; Kemppinen, Anu; Cotsapas, Chris; Shah, Tejas S.; Spencer, Chris; Booth, David and Goris, An, et al. (2013) In Nature Genetics 45(11). p.1353-1353
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 x 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 x 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... (More)
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 x 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 x 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. (Less)
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Nature Genetics
volume
45
issue
11
pages
1353 - 1353
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Nature Publishing Group
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  • wos:000326384100016
  • scopus:84887058596
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1546-1718
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10.1038/ng.2770
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English
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2014-01-03 10:41:53
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@article{5d7dd921-304d-4c2f-90ef-5aabe0e822f8,
  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 &lt; 1.0 x 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 &lt; 5.0 x 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.},
  author       = {Beecham, Ashley H. and Patsopoulos, Nikolaos A. and Xifara, Dionysia K. and Davis, Mary F. and Kemppinen, Anu and Cotsapas, Chris and Shah, Tejas S. and Spencer, Chris and Booth, David and Goris, An and Oturai, Annette and Saarela, Janna and Fontaine, Bertrand and Hemmer, Bernhard and Martin, Claes and Zipp, Frauke and D'Alfonso, Sandra and Martinelli-Boneschi, Filippo and Taylor, Bruce and Harbo, Hanne F. and Kockum, Ingrid and Hillert, Jan and Olsson, Tomas and Ban, Maria and Oksenberg, Jorge R. and Hintzen, Rogier and Barcellos, Lisa F. and Agliardi, Cristina and Alfredsson, Lars and Alizadeh, Mehdi and Anderson, Carl and Andrews, Robert and Sondergaard, Helle Bach and Baker, Amie and Band, Gavin and Baranzini, Sergio E. and Barizzone, Nadia and Barrett, Jeffrey and Bellenguez, Celine and Bergamaschi, Laura and Bernardinelli, Luisa and Berthele, Achim and Biberacher, Viola and Binder, Thomas M. C. and Blackburn, Hannah and Bomfim, Izaura L. and Brambilla, Paola and Broadley, Simon and Brochet, Bruno and Brundin, Lou and Buck, Dorothea and Butzkueven, Helmut and Caillier, Stacy J. and Camu, William and Carpentier, Wassila and Cavalla, Paola and Celius, Elisabeth G. and Coman, Irene and Comi, Giancarlo and Corrado, Lucia and Cosemans, Leentje and Cournu-Rebeix, Isabelle and Cree, Bruce A. C. and Cusi, Daniele and Damotte, Vincent and Defer, Gilles and Delgado, Silvia R. and Deloukas, Panos and di Sapio, Alessia and Dilthey, Alexander T. and Donnelly, Peter and Dubois, Benedicte and Duddy, Martin and Edkins, Sarah and Elovaara, Irina and Esposito, Federica and Evangelou, Nikos and Fiddes, Barnaby and Field, Judith and Franke, Andre and Freeman, Colin and Frohlich, Irene Y. and Galimberti, Daniela and Gieger, Christian and Gourraud, Pierre-Antoine and Graetz, Christiane and Graham, Andrew and Grummel, Verena and Guaschino, Clara and Hadjixenofontos, Athena and Hakonarson, Hakon and Halfpenny, Christopher and Hall, Gillian and Hall, Per and Hamsten, Anders and Harley, James and Harrower, Timothy and Hawkins, Clive and Hellenthal, Garrett and Hillier, Charles and Hobart, Jeremy and Hoshi, Muni and Hunt, Sarah E. and Jagodic, Maja and Jelcic, Ilijas and Jochim, Angela and Kendall, Brian and Kermode, Allan and Kilpatrick, Trevor and Koivisto, Keijo and Konidari, Ioanna and Korn, Thomas and Kronsbein, Helena and Langford, Cordelia and Larsson, Malin and Lathrop, Mark and Lebrun-Frenay, Christine and Lechner-Scott, Jeannette and Lee, Michelle H. and Leone, Maurizio A. and Leppa, Virpi and Liberatore, Giuseppe and Lie, Benedicte A. and Lill, Christina M. and Linden, Magdalena and Link, Jenny and Luessi, Felix and Lycke, Jan and Macciardi, Fabio and Mannisto, Satu and Manrique, Clara P. and Martin, Roland and Martinelli, Vittorio and Mason, Deborah and Mazibrada, Gordon and McCabe, Cristin and Mero, Inger-Lise and Mescheriakova, Julia and Moutsianas, Loukas and Myhr, Kjell-Morten and Nagels, Guy and Nicholas, Richard and Nilsson, Petra and Piehl, Fredrik and Pirinen, Matti and Price, Sian E. and Quach, Hong and Reunanen, Mauri and Robberecht, Wim and Robertson, Neil P. and Rodegher, Mariaemma and Rog, David and Salvetti, Marco and Schnetz-Boutaud, Nathalie C. and Sellebjerg, Finn and Selter, Rebecca C. and Schaefer, Catherine and Shaunak, Sandip and Shen, Ling and Shields, Simon and Siffrin, Volker and Slee, Mark and Sorensen, Per Soelberg and Sorosina, Melissa and Sospedra, Mireia and Spurkland, Anne and Strange, Amy and Sundqvist, Emilie and Thijs, Vincent and Thorpe, John and Ticca, Anna and Tienari, Pentti and van Duijn, Cornelia and Visser, Elizabeth M. and Vucic, Steve and Westerlind, Helga and Wiley, James S. and Wilkins, Alastair and Wilson, James F. and Winkelmann, Juliane and Zajicek, John and Zindler, Eva and Haines, Jonathan L. and Pericak-Vance, Margaret A. and Ivinson, Adrian J. and Stewart, Graeme and Hafler, David and Hauser, Stephen L. and Compston, Alastair and McVean, Gil and De Jager, Philip and Sawcer, Stephen J. and McCauley, Jacob L.},
  issn         = {1546-1718},
  language     = {eng},
  number       = {11},
  pages        = {1353--1353},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis},
  url          = {http://dx.doi.org/10.1038/ng.2770},
  volume       = {45},
  year         = {2013},
}