Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis
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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; 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; 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 M C; 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, Irène; Comi, Giancarlo; Corrado, Lucia; Cosemans, Leentje; Cournu-Rebeix, Isabelle; Cree, Bruce A C; 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; 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; 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; International Multiple Sclerosis Genetics Consortium (IMSGC).
in: NAT GENET, Jahrgang 45, Nr. 11, 01.11.2013, S. 1353-60.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis
AU - Beecham, Ashley H
AU - Patsopoulos, Nikolaos A
AU - Xifara, Dionysia K
AU - Davis, Mary F
AU - Kemppinen, Anu
AU - Cotsapas, Chris
AU - Shah, Tejas S
AU - Spencer, Chris
AU - Booth, David
AU - Goris, An
AU - Oturai, Annette
AU - Saarela, Janna
AU - Fontaine, Bertrand
AU - Hemmer, Bernhard
AU - Martin, Claes
AU - Zipp, Frauke
AU - D'Alfonso, Sandra
AU - Martinelli-Boneschi, Filippo
AU - Taylor, Bruce
AU - Harbo, Hanne F
AU - Kockum, Ingrid
AU - Hillert, Jan
AU - Olsson, Tomas
AU - Ban, Maria
AU - Oksenberg, Jorge R
AU - Hintzen, Rogier
AU - Barcellos, Lisa F
AU - Agliardi, Cristina
AU - Alfredsson, Lars
AU - Alizadeh, Mehdi
AU - Anderson, Carl
AU - Andrews, Robert
AU - Søndergaard, Helle Bach
AU - Baker, Amie
AU - Band, Gavin
AU - Baranzini, Sergio E
AU - Barizzone, Nadia
AU - Barrett, Jeffrey
AU - Bellenguez, Céline
AU - Bergamaschi, Laura
AU - Bernardinelli, Luisa
AU - Berthele, Achim
AU - Biberacher, Viola
AU - Binder, Thomas M C
AU - Blackburn, Hannah
AU - Bomfim, Izaura L
AU - Brambilla, Paola
AU - Broadley, Simon
AU - Brochet, Bruno
AU - Brundin, Lou
AU - Buck, Dorothea
AU - Butzkueven, Helmut
AU - Caillier, Stacy J
AU - Camu, William
AU - Carpentier, Wassila
AU - Cavalla, Paola
AU - Celius, Elisabeth G
AU - Coman, Irène
AU - Comi, Giancarlo
AU - Corrado, Lucia
AU - Cosemans, Leentje
AU - Cournu-Rebeix, Isabelle
AU - Cree, Bruce A C
AU - Cusi, Daniele
AU - Damotte, Vincent
AU - Defer, Gilles
AU - Delgado, Silvia R
AU - Deloukas, Panos
AU - di Sapio, Alessia
AU - Dilthey, Alexander T
AU - Donnelly, Peter
AU - Dubois, Bénédicte
AU - Duddy, Martin
AU - Edkins, Sarah
AU - Elovaara, Irina
AU - Esposito, Federica
AU - Evangelou, Nikos
AU - Fiddes, Barnaby
AU - Field, Judith
AU - Franke, Andre
AU - Freeman, Colin
AU - Frohlich, Irene Y
AU - Galimberti, Daniela
AU - Gieger, Christian
AU - Gourraud, Pierre-Antoine
AU - Graetz, Christiane
AU - Graham, Andrew
AU - Grummel, Verena
AU - Guaschino, Clara
AU - Hadjixenofontos, Athena
AU - Hakonarson, Hakon
AU - Halfpenny, Christopher
AU - Hall, Gillian
AU - Hall, Per
AU - Hamsten, Anders
AU - Harley, James
AU - Harrower, Timothy
AU - Hawkins, Clive
AU - Hellenthal, Garrett
AU - Hillier, Charles
AU - Hobart, Jeremy
AU - Hoshi, Muni
AU - Hunt, Sarah E
AU - Jagodic, Maja
AU - Jelcic, Ilijas
AU - Jochim, Angela
AU - Kendall, Brian
AU - Kermode, Allan
AU - Kilpatrick, Trevor
AU - Koivisto, Keijo
AU - Konidari, Ioanna
AU - Korn, Thomas
AU - Kronsbein, Helena
AU - Langford, Cordelia
AU - Larsson, Malin
AU - Lathrop, Mark
AU - Lebrun-Frenay, Christine
AU - Lechner-Scott, Jeannette
AU - Lee, Michelle H
AU - Leone, Maurizio A
AU - Leppä, Virpi
AU - Liberatore, Giuseppe
AU - Lie, Benedicte A
AU - Lill, Christina M
AU - Lindén, Magdalena
AU - Link, Jenny
AU - Luessi, Felix
AU - Lycke, Jan
AU - Macciardi, Fabio
AU - Männistö, Satu
AU - Manrique, Clara P
AU - Martin, Roland
AU - Martinelli, Vittorio
AU - Mason, Deborah
AU - Mazibrada, Gordon
AU - McCabe, Cristin
AU - Mero, Inger-Lise
AU - Mescheriakova, Julia
AU - Moutsianas, Loukas
AU - Myhr, Kjell-Morten
AU - Nagels, Guy
AU - Nicholas, Richard
AU - Nilsson, Petra
AU - Piehl, Fredrik
AU - Pirinen, Matti
AU - Price, Siân E
AU - Quach, Hong
AU - Reunanen, Mauri
AU - Robberecht, Wim
AU - Robertson, Neil P
AU - Rodegher, Mariaemma
AU - Rog, David
AU - Salvetti, Marco
AU - Schnetz-Boutaud, Nathalie C
AU - Sellebjerg, Finn
AU - Selter, Rebecca C
AU - Schaefer, Catherine
AU - Shaunak, Sandip
AU - Shen, Ling
AU - Shields, Simon
AU - Siffrin, Volker
AU - Slee, Mark
AU - Sorensen, Per Soelberg
AU - Sorosina, Melissa
AU - Sospedra, Mireia
AU - Spurkland, Anne
AU - Strange, Amy
AU - Sundqvist, Emilie
AU - Thijs, Vincent
AU - Thorpe, John
AU - Ticca, Anna
AU - Tienari, Pentti
AU - van Duijn, Cornelia
AU - Visser, Elizabeth M
AU - Vucic, Steve
AU - Westerlind, Helga
AU - Wiley, James S
AU - Wilkins, Alastair
AU - Wilson, James F
AU - Winkelmann, Juliane
AU - Zajicek, John
AU - Zindler, Eva
AU - Haines, Jonathan L
AU - Pericak-Vance, Margaret A
AU - Ivinson, Adrian J
AU - Stewart, Graeme
AU - Hafler, David
AU - Hauser, Stephen L
AU - Compston, Alastair
AU - McVean, Gil
AU - De Jager, Philip
AU - Sawcer, Stephen J
AU - McCauley, Jacob L
AU - International Multiple Sclerosis Genetics Consortium (IMSGC)
PY - 2013/11/1
Y1 - 2013/11/1
N2 - 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.
AB - 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.
KW - Chromosome Mapping
KW - European Continental Ancestry Group
KW - Gene Frequency
KW - Genetic Loci
KW - Genetic Predisposition to Disease
KW - Genetic Variation
KW - Genome-Wide Association Study
KW - Genotype
KW - Humans
KW - Multiple Sclerosis
KW - Polymorphism, Single Nucleotide
U2 - 10.1038/ng.2770
DO - 10.1038/ng.2770
M3 - SCORING: Journal article
C2 - 24076602
VL - 45
SP - 1353
EP - 1360
JO - NAT GENET
JF - NAT GENET
SN - 1061-4036
IS - 11
ER -