Skip to main content
eScholarship
Open Access Publications from the University of California

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

  • Author(s): International Multiple Sclerosis Genetics Consortium (IMSGC)
  • 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
  • Wellcome Trust Case Control Consortium 2 (WTCCC2)
  • International IBD Genetics Consortium (IIBDGC)
  • Agliardi, Cristina
  • Alfredsson, Lars
  • Alizadeh, Mehdi
  • Anderson, Carl
  • Andrews, Robert
  • Søndergaard, Helle Bach
  • Baker, Amie
  • Band, Gavin
  • Baranzini, Sergio E
  • Barizzone, Nadia
  • Barrett, Jeffrey
  • Bellenguez, Céline
  • Bergamaschi, Laura
  • Bernardinelli, Luisa
  • Berthele, Achim
  • Biberacher, Viola
  • Binder, Thomas MC
  • Blackburn, Hannah
  • Bomfim, Izaura L
  • Brambilla, Paola
  • Broadley, Simon
  • Brochet, Bruno
  • Brundin, Lou
  • Brundin, Lou
  • Buck, Dorothea
  • Butzkueven, Helmut
  • Caillier, Stacy J
  • Camu, William
  • Carpentier, Wassila
  • Cavalla, Paola
  • Celius, Elisabeth G
  • Coman, Irène
  • 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
  • Hobart, Jeremy
  • Hoshi, Muni
  • Hunt, Sarah E
  • Jagodic, Maja
  • Jelčić, 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
  • Leppä, Virpi
  • Liberatore, Giuseppe
  • Lie, Benedicte A
  • Lill, Christina M
  • Lindén, Magdalena
  • Link, Jenny
  • Luessi, Felix
  • Lycke, Jan
  • Macciardi, Fabio
  • Männistö, 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, Siân 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
  • et al.

Published Web Location

https://doi.org/10.1038/ng.2770Creative Commons 'BY' version 4.0 license
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.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
Current View