Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis
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Author(s)
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
Saarela, Janna
Fontaine, Bertrand
Hemmer, Bernhard
Martin, Claes
Zipp, Frauke
D'Alfonso, Sandra
Martinelli-Boneschi, Filippo
Taylor, Bruce
Harbo, Hanne F
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, Benedicte
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
Hobart, Jeremy
Hoshi, Muni
Hunt, Sarah E
Jagodic, Maja
Jelcic, Ilijas
Jochim, Angela
Kendall, Brian
Kermode, Allan
Kilpatrick, Trevor
Koivisto, Keijo
Konidari, Ioanna
Korn, Thomas
Kronsbein, Helena
Langford, Cordelia
Larsson, Malin
Lathrop, Mark
Lebrun-Frenay, Christine
Lechner-Scott, Jeannette
Lee, Michelle H
Leone, Maurizio A
Leppa, Virpi
Liberatore, Giuseppe
Lie, Benedicte A
Lill, Christina M
Linden, Magdalena
Link, Jenny
Luessi, Felix
Lycke, Jan
Macciardi, Fabio
Mannisto, Satu
Manrique, Clara P
Martin, Roland
Martinelli, Vittorio
Mason, Deborah
Mazibrada, Gordon
McCabe, Cristin
Mero, Inger-Lise
Mescheriakova, Julia
Moutsianas, Loukas
Myhr, Kjell-Morten
Nagels, Guy
Nicholas, Richard
Nilsson, Petra
Piehl, Fredrik
Pirinen, Matti
Price, Sian E
Quach, Hong
Reunanen, Mauri
Robberecht, Wim
Robertson, Neil P
Rodegher, Mariaemma
Rog, David
Salvetti, Marco
Schnetz-Boutaud, Nathalie C
Sellebjerg, Finn
Selter, Rebecca C
Schaefer, Catherine
Shaunak, Sandip
Shen, Ling
Shields, Simon
Siffrin, Volker
Slee, Mark
Sorensen, Per Soelberg
Sorosina, Melissa
Sospedra, Mireia
Spurkland, Anne
Strange, Amy
Sundqvist, Emilie
Thijs, Vincent
Thorpe, John
Ticca, Anna
Tienari, Pentti
van Duijn, Cornelia
Visser, Elizabeth M
Vucic, Steve
Westerlind, Helga
Wiley, James S
Wilkins, Alastair
Wilson, James F
Winkelmann, Juliane
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
De Jager, Philip
Sawcer, Stephen J
McCauley, Jacob L
Griffith University Author(s)
Year published
2013
Metadata
Show full item recordAbstract
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 נ10-4). 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 נ10-8), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 ...
View 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 נ10-4). 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 נ10-8), 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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View 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 נ10-4). 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 נ10-8), 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.
View less >
Journal Title
Nature Genetics
Volume
45
Issue
11
Copyright Statement
© 2013 Nature Publishing Group. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal website for access to the definitive, published version.
Subject
Biological sciences
Biomedical and clinical sciences