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

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

doi:10.1038/ng.2770

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

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

Department of Clinical Medicine

796 Citations (Scopus)

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.

Original language	English
Journal	Nature Genetics
Volume	45
Issue number	11
Pages (from-to)	1353-1360
Number of pages	8
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.2770
Publication status	Published - Nov 2013

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10.1038/ng.2770

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Beecham, A. H., Patsopoulos, N. A., Xifara, D. K., Davis, M. F., Kemppinen, A., Cotsapas, C., Shah, T. S., Spencer, C., Booth, D., Goris, A., Oturai, A., Saarela, J., Fontaine, B., Hemmer, B., Martin, C., Zipp, F., D'Alfonso, S., Martinelli-Boneschi, F., Taylor, B., ... (IMSGC), I. M. S. G. C. (2013). Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nature Genetics, 45(11), 1353-1360. https://doi.org/10.1038/ng.2770

Beecham, AH, Patsopoulos, NA, Xifara, DK, Davis, MF, Kemppinen, A, Cotsapas, C, Shah, TS, Spencer, C, Booth, D, Goris, A, Oturai, A, Saarela, J, Fontaine, B, Hemmer, B, Martin, C, Zipp, F, D'Alfonso, S, Martinelli-Boneschi, F, Taylor, B, Harbo, HF, Kockum, I, Hillert, J, Olsson, T, Ban, M, Oksenberg, JR, Hintzen, R, Barcellos, LF, Agliardi, C, Alfredsson, L, Alizadeh, M, Anderson, C, Andrews, R, Søndergaard, HB, Baker, A, Band, G, Baranzini, SE, Barizzone, N, Barrett, J, Bellenguez, C, Bergamaschi, L, Bernardinelli, L, Berthele, A, Biberacher, V, Binder, T, Blackburn, H, Bomfim, IL, Brambilla, P, Broadley, S, Brochet, B, Brundin, L, Buck, D, Butzkueven, H, Caillier, SJ, Camu, W, Carpentier, W, Cavalla, P, Celius, EG, Coman, I, Comi, G, Corrado, L, Cosemans, L, Cournu-Rebeix, I, Cree, BAC, Cusi, D, Damotte, V, Defer, G, Delgado, SR, Deloukas, P, di Sapio, A, Dilthey, AT, Donnelly, P, Dubois, B, Duddy, M, Edkins, S, Elovaara, I, Esposito, F, Evangelou, N, Fiddes, B, Field, J, Franke, A, Freeman, C, Frohlich, IY, Galimberti, D, Gieger, C, Gourraud, P-A, Graetz, C, Graham, A, Grummel, V, Guaschino, C, Hadjixenofontos, A, Hakonarson, H, Halfpenny, C, Hall, G, Hall, P, Hamsten, A, Harley, J, Harrower, T, Hawkins, C, Hellenthal, G, Hillier, C, Hobart, J, Hoshi, M, Hunt, SE, Jagodic, M, Jel?i?, I, Jochim, A, Kendall, B, Kermode, A, Kilpatrick, T, Koivisto, K, Konidari, I, Korn, T, Kronsbein, H, Langford, C, Larsson, M, Lathrop, M, Lebrun-Frenay, C, Lechner-Scott, J, Lee, MH, Leone, MA, Leppä, V, Liberatore, G, Lie, BA, Lill, CM, Lindén, M, Link, J, Luessi, F, Lycke, J, Macciardi, F, Männistö, S, Manrique, CP, Martin, R, Martinelli, V, Mason, D, Mazibrada, G, McCabe, C, Mero, I-L, Mescheriakova, J, Moutsianas, L, Myhr, K-M, Nagels, G, Nicholas, R, Nilsson, P, Piehl, F, Pirinen, M, Price, SE, Quach, H, Reunanen, M, Robberecht, W, Robertson, NP, Rodegher, M, Rog, D, Salvetti, M, Schnetz-Boutaud, NC, Sellebjerg, F, Selter, RC, Schaefer, C, Shaunak, S, Shen, L, Shields, S, Siffrin, V, Slee, M, Sorensen, PS, Sorosina, M, Sospedra, M, Spurkland, A, Strange, A, Sundqvist, E, Thijs, V, Thorpe, J, Ticca, A, Tienari, P, van Duijn, C, Visser, EM, Vucic, S, Westerlind, H, Wiley, JS, Wilkins, A, Wilson, J, Winkelmann, J, Zajicek, J, Zindler, E, Haines, JL, Pericak-Vance, MA, Ivinson, AJ, Stewart, G, Hafler, D, Hauser, SL, Compston, A, McVean, G, De Jager, P, Sawcer, SJ, McCauley, JL & (IMSGC), IMSGC 2013, 'Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis', Nature Genetics, vol. 45, no. 11, pp. 1353-1360. https://doi.org/10.1038/ng.2770

@article{d91e33bc75af4952b5a12033358a0b72,

title = "Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis",

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.",

author = "Beecham, {Ashley H} and Patsopoulos, {Nikolaos A} and Xifara, {Dionysia K} and Davis, {Mary F} and Anu Kemppinen and Chris Cotsapas and Shah, {Tejas S} and Chris Spencer and David Booth and An Goris and Annette Oturai and Janna Saarela and Bertrand Fontaine and Bernhard Hemmer and Claes Martin and Frauke Zipp and Sandra D'Alfonso and Filippo Martinelli-Boneschi and Bruce Taylor and Harbo, {Hanne F} and Ingrid Kockum and Jan Hillert and Tomas Olsson and Maria Ban and Oksenberg, {Jorge R} and Rogier Hintzen and Barcellos, {Lisa F} and Cristina Agliardi and Lars Alfredsson and Mehdi Alizadeh and Carl Anderson and Robert Andrews and S{\o}ndergaard, {Helle Bach} and Amie Baker and Gavin Band and Baranzini, {Sergio E} and Nadia Barizzone and Jeffrey Barrett and C{\'e}line Bellenguez and Laura Bergamaschi and Luisa Bernardinelli and Achim Berthele and Viola Biberacher and Thomas Binder and Hannah Blackburn and Bomfim, {Izaura L} and Paola Brambilla and Simon Broadley and Bruno Brochet and Lou Brundin and Dorothea Buck and Helmut Butzkueven and Caillier, {Stacy J} and William Camu and Wassila Carpentier and Paola Cavalla and Celius, {Elisabeth G} and Ir{\`e}ne Coman and Giancarlo Comi and Lucia Corrado and Leentje Cosemans and Isabelle Cournu-Rebeix and Cree, {Bruce A C} and Daniele Cusi and Vincent Damotte and Gilles Defer and Delgado, {Silvia R} and Panos Deloukas and {di Sapio}, Alessia and Dilthey, {Alexander T} and Peter Donnelly and B{\'e}n{\'e}dicte Dubois and Martin Duddy and Sarah Edkins and Irina Elovaara and Federica Esposito and Nikos Evangelou and Barnaby Fiddes and Judith Field and Andre Franke and Colin Freeman and Frohlich, {Irene Y} and Daniela Galimberti and Christian Gieger and Pierre-Antoine Gourraud and Christiane Graetz and Andrew Graham and Verena Grummel and Clara Guaschino and Athena Hadjixenofontos and Hakon Hakonarson and Christopher Halfpenny and Gillian Hall and Per Hall and Anders Hamsten and James Harley and Timothy Harrower and Clive Hawkins and Garrett Hellenthal and Charles Hillier and Jeremy Hobart and Muni Hoshi and Hunt, {Sarah E} and Maja Jagodic and Ilijas Jel?i? and Angela Jochim and Brian Kendall and Allan Kermode and Trevor Kilpatrick and Keijo Koivisto and Ioanna Konidari and Thomas Korn and Helena Kronsbein and Cordelia Langford and Malin Larsson and Mark Lathrop and Christine Lebrun-Frenay and Jeannette Lechner-Scott and Lee, {Michelle H} and Leone, {Maurizio A} and Virpi Lepp{\"a} and Giuseppe Liberatore and Lie, {Benedicte A} and Lill, {Christina M} and Magdalena Lind{\'e}n and Jenny Link and Felix Luessi and Jan Lycke and Fabio Macciardi and Satu M{\"a}nnist{\"o} and Manrique, {Clara P} and Roland Martin and Vittorio Martinelli and Deborah Mason and Gordon Mazibrada and Cristin McCabe and Inger-Lise Mero and Julia Mescheriakova and Loukas Moutsianas and Kjell-Morten Myhr and Guy Nagels and Richard Nicholas and Petra Nilsson and Fredrik Piehl and Matti Pirinen and Price, {Si{\^a}n E} and Hong Quach and Mauri Reunanen and Wim Robberecht and Robertson, {Neil P} and Mariaemma Rodegher and David Rog and Marco Salvetti and Schnetz-Boutaud, {Nathalie C} and Finn Sellebjerg and Selter, {Rebecca C} and Catherine Schaefer and Sandip Shaunak and Ling Shen and Simon Shields and Volker Siffrin and Mark Slee and Sorensen, {Per Soelberg} and Melissa Sorosina and Mireia Sospedra and Anne Spurkland and Amy Strange and Emilie Sundqvist and Vincent Thijs and John Thorpe and Anna Ticca and Pentti Tienari and {van Duijn}, Cornelia and Visser, {Elizabeth M} and Steve Vucic and Helga Westerlind and Wiley, {James S} and Alastair Wilkins and James Wilson and Juliane Winkelmann and John Zajicek and Eva Zindler and Haines, {Jonathan L} and Pericak-Vance, {Margaret A} and Ivinson, {Adrian J} and Graeme Stewart and David Hafler and Hauser, {Stephen L} and Alastair Compston and Gil McVean and {De Jager}, Philip and Sawcer, {Stephen J} and McCauley, {Jacob L} and (IMSGC), {International Multiple Sclerosis Genetics Consortium}",

year = "2013",

month = nov,

doi = "10.1038/ng.2770",

language = "English",

volume = "45",

pages = "1353--1360",

journal = "Nature: New biology",

issn = "1061-4036",

publisher = "nature publishing group",

number = "11",

}

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

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 - Jel?i?, 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

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 - (IMSGC), International Multiple Sclerosis Genetics Consortium

PY - 2013/11

Y1 - 2013/11

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.

U2 - 10.1038/ng.2770

DO - 10.1038/ng.2770

M3 - Letter

SN - 1061-4036

VL - 45

SP - 1353

EP - 1360

JO - Nature: New biology

JF - Nature: New biology

IS - 11

ER -

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

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