ITEM METADATA RECORD
Title: Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
Authors: International Multiple Sclerosis Genetics Consortium *
Wellcome Trust Case Control Consortium 2 *
Sawcer, Stephen *
Hellenthal, Garrett *
Pirinen, Matti *
Spencer, Chris C A *
Patsopoulos, Nikolaos A
Moutsianas, Loukas
Dilthey, Alexander
Su, Zhan
Freeman, Colin
Hunt, Sarah E
Edkins, Sarah
Gray, Emma
Booth, David R
Potter, Simon C
Goris, An
Band, Gavin
Oturai, Annette Bang
Strange, Amy
Saarela, Janna
Bellenguez, Céline
Fontaine, Bertrand
Gillman, Matthew
Hemmer, Bernhard
Gwilliam, Rhian
Zipp, Frauke
Jayakumar, Alagurevathi
Martin, Roland
Leslie, Stephen
Hawkins, Stanley
Giannoulatou, Eleni
D'alfonso, Sandra
Blackburn, Hannah
Martinelli Boneschi, Filippo
Liddle, Jennifer
Harbo, Hanne F
Perez, Marc L
Spurkland, Anne
Waller, Matthew J
Mycko, Marcin P
Ricketts, Michelle
Comabella, Manuel
Hammond, Naomi
Kockum, Ingrid
McCann, Owen T
Ban, Maria
Whittaker, Pamela
Kemppinen, Anu
Weston, Paul
Hawkins, Clive
Widaa, Sara
Zajicek, John
Dronov, Serge
Robertson, Neil
Bumpstead, Suzannah J
Barcellos, Lisa F
Ravindrarajah, Rathi
Abraham, Roby
Alfredsson, Lars
Ardlie, Kristin
Aubin, Cristin
Baker, Amie
Baker, Katharine
Baranzini, Sergio E
Bergamaschi, Laura
Bergamaschi, Roberto
Bernstein, Allan
Berthele, Achim
Boggild, Mike
Bradfield, Jonathan P
Brassat, David
Broadley, Simon A
Buck, Dorothea
Butzkueven, Helmut
Capra, Ruggero
Carroll, William M
Cavalla, Paola
Celius, Elisabeth G
Cepok, Sabine
Chiavacci, Rosetta
Clerget-Darpoux, Françoise
Clysters, Katleen
Comi, Giancarlo
Cossburn, Mark
Cournu-Rebeix, Isabelle
Cox, Mathew B
Cozen, Wendy
Cree, Bruce A C
Cross, Anne H
Cusi, Daniele
Daly, Mark J
Davis, Emma
de Bakker, Paul I W
Debouverie, Marc
D'hooghe, Marie Beatrice
Dixon, Katherine
Dobosi, Rita
Dubois, Bénédicte
Ellinghaus, David
Elovaara, Irina
Esposito, Federica
Fontenille, Claire
Foote, Simon
Franke, Andre
Galimberti, Daniela
Ghezzi, Angelo
Glessner, Joseph
Gomez, Refujia
Gout, Olivier
Graham, Colin
Grant, Struan F A
Guerini, Franca Rosa
Hakonarson, Hakon
Hall, Per
Hamsten, Anders
Hartung, Hans-Peter
Heard, Rob N
Heath, Simon
Hobart, Jeremy
Hoshi, Muna
Infante-Duarte, Carmen
Ingram, Gillian
Ingram, Wendy
Islam, Talat
Jagodic, Maja
Kabesch, Michael
Kermode, Allan G
Kilpatrick, Trevor J
Kim, Cecilia
Klopp, Norman
Koivisto, Keijo
Larsson, Malin
Lathrop, Mark
Lechner-Scott, Jeannette S
Leone, Maurizio A
Leppä, Virpi
Liljedahl, Ulrika
Bomfim, Izaura Lima
Lincoln, Robin R
Link, Jenny
Liu, Jianjun
Lorentzen, Aslaug R
Lupoli, Sara
Macciardi, Fabio
Mack, Thomas
Marriott, Mark
Martinelli, Vittorio
Mason, Deborah
McCauley, Jacob L
Mentch, Frank
Mero, Inger-Lise
Mihalova, Tania
Montalban, Xavier
Mottershead, John
Myhr, Kjell-Morten
Naldi, Paola
Ollier, William
Page, Alison
Palotie, Aarno
Pelletier, Jean
Piccio, Laura
Pickersgill, Trevor
Piehl, Fredrik
Pobywajlo, Susan
Quach, Hong L
Ramsay, Patricia P
Reunanen, Mauri
Reynolds, Richard
Rioux, John D
Rodegher, Mariaemma
Roesner, Sabine
Rubio, Justin P
Rückert, Ina-Maria
Salvetti, Marco
Salvi, Erika
Santaniello, Adam
Schaefer, Catherine A
Schreiber, Stefan
Schulze, Christian
Scott, Rodney J
Sellebjerg, Finn
Selmaj, Krzysztof W
Sexton, David
Shen, Ling
Simms-Acuna, Brigid
Skidmore, Sheila
Sleiman, Patrick M A
Smestad, Cathrine
Sørensen, Per Soelberg
Søndergaard, Helle Bach
Stankovich, Jim
Strange, Richard C
Sulonen, Anna-Maija
Sundqvist, Emilie
Syvänen, Ann-Christine
Taddeo, Francesca
Taylor, Bruce
Blackwell, Jenefer M
Tienari, Pentti
Bramon, Elvira
Tourbah, Ayman
Brown, Matthew A
Tronczynska, Ewa
Casas, Juan P
Tubridy, Niall
Corvin, Aiden
Vickery, Jane
Jankowski, Janusz
Villoslada, Pablo
Markus, Hugh S
Wang, Kai
Mathew, Christopher G
Wason, James
Palmer, Colin N A
Wichmann, H-Erich
Plomin, Robert
Willoughby, Ernest
Rautanen, Anna
Winkelmann, Juliane
Wittig, Michael
Trembath, Richard C
Yaouanq, Jacqueline
Viswanathan, Ananth C
Zhang, Haitao
Wood, Nicholas W
Zuvich, Rebecca
Deloukas, Panos
Langford, Cordelia
Duncanson, Audrey
Oksenberg, Jorge R
Pericak-Vance, Margaret A
Haines, Jonathan L
Olsson, Tomas
Hillert, Jan
Ivinson, Adrian J
De Jager, Philip L
Peltonen, Leena
Stewart, Graeme J
Hafler, David A
Hauser, Stephen L
McVean, Gil
Donnelly, Peter #
Compston, Alastair # ×
Issue Date: Aug-2011
Publisher: Nature Publishing Group
Series Title: Nature vol:476 issue:7359 pages:214-9
Article number: 10.1038/nature10251
Abstract: Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
URI: 
ISSN: 0028-0836
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Neuroimmunology
* (joint) first author
× corresponding author
# (joint) last author

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