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

Ashley Beecham; Nikolaos Patsopoulos; Dionysia Xifara; Mary Davis; Anu Kemppinen; Chris Cotsapas; Tejas Shah; Chris Spencer; David J Booth; An Goris; Annette Oturai; Janna Saarela; Bertrand Fontaine; Bernhard Hemmer; Claes Martin; Frauke Zipp; Sandra d'Alfonso; Filippo Martinelli-Boneschi; Bruce Taylor; Hanne Flinstad Harbo; Ingrid Kockum; Jan Hillert; Tomas Olsson; Maria Ban; Jorge R Oksenberg; Rogier Hintzen; Lisa 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 Bomfim; Paola Brambilla; Simon Broadley; Bruno Brochet; Lou Brundin; Dorothea Buck; Helmut Butzkueven; Stacy J Caillier; William Camu; Wassila Carpentier; Paola Cavalla; Elisabeth Celius; Irène Coman; Giancarlo Comi; Lucia Corrado; Leentje Cosemans; Isabelle Cournu-Rebeix; Bruce Cree; Daniele Cusi; Vincent Damotte; Gilles Defer; Silvia 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 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 Hunt; Maja Jagodic; Ilijas Jelčić; 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 Lee; Maurizio Leone; Virpi Leppä; Giuseppe Liberatore; Benedicte Lie; Christina Lill; Magdalena Lindén; Jenny Link; Felix Luessi; Jan Lycke; Fabio Macciardi; Satu Männistö; Clara 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 Price; Hong Quach; Mauri Reunanen; Wim Robberecht; Neil Robertson; Mariaemma Rodegher; David Rog; Marco Salvetti; Nathalie Schnetz-Boutaud; Finn Sellebjerg; Rebecca 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 M. van Duijn; Elizabeth Visser; Steve Vucic; Helga Westerlind; James Wiley; Alastair Wilkins; James Wilson; Juliane Winkelmann; John Zajicek; Eva Zindler; Jonathan L. Haines; Margaret Pericak-Vance; Adrian Ivinson; Graeme Stewart; David A Hafler; Stephen Hauser; Alastair Compston; Gil Mcvean; Philip L de Jager; Stephen Sawcer; Jacob Mccauley

doi:10.1038/ng.2770

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

Journal article

Peer reviewed

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

Ashley Beecham, Nikolaos Patsopoulos, Dionysia Xifara, Mary Davis, Anu Kemppinen, Chris Cotsapas, Tejas Shah, Chris Spencer, David J Booth, An Goris, …

Nature Genetics, Vol.45(11), pp.1353-1360

11/2013

DOI: https://doi.org/10.1038/ng.2770

PMCID: PMC3832895

PMID: 24076602

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.

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Title: Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis
Creators - without role: Ashley Beecham - University of Miami
Nikolaos Patsopoulos - Harvard University Press
Dionysia Xifara - University of Oxford
Mary Davis
Anu Kemppinen - University of Cambridge
Chris Cotsapas - Broad Institute
Tejas Shah
Chris Spencer
David J Booth - University of Sydney
An Goris - KU Leuven
Annette Oturai - University of Copenhagen
Janna Saarela - University of Helsinki
Bertrand Fontaine - Institut du Cerveau
Bernhard Hemmer - Technical University of Munich
Claes Martin - Karolinska Institutet
Frauke Zipp - Johannes Gutenberg University Mainz
Sandra d'Alfonso
Filippo Martinelli-Boneschi
Bruce Taylor - University of Tasmania
Hanne Flinstad Harbo - University of Oslo
Ingrid Kockum - Karolinska Institutet
Jan Hillert - Karolinska Institutet
Tomas Olsson - Karolinska Institutet
Maria Ban - University of Cambridge
Jorge R Oksenberg - University of California, San Francisco
Rogier Hintzen - Erasmus University Rotterdam
Lisa Barcellos - University of California, Berkeley
Cristina Agliardi
Lars Alfredsson - Karolinska Institutet
Mehdi Alizadeh - Université de Rennes
Carl Anderson - Michigan Technological University
Robert Andrews
Helle Bach Søndergaard - University of Copenhagen
Amie Baker - University of Cambridge
Gavin Band - University of Oxford
Sergio E Baranzini - University of California, San Francisco
Nadia Barizzone - Università degli Studi del Piemonte Orientale “Amedeo Avogadro”
Jeffrey Barrett - Wellcome Sanger Institute
Céline Bellenguez - University of Oxford
Laura Bergamaschi - Università degli Studi del Piemonte Orientale “Amedeo Avogadro”
Luisa Bernardinelli - Medical Research Council
Achim Berthele - Technical University of Munich
Viola Biberacher - Technical University of Munich
Thomas Binder
Hannah Blackburn
Izaura Bomfim - Karolinska Institutet
Paola Brambilla
Simon Broadley - Griffith University
Bruno Brochet - Université de Bordeaux
Lou Brundin - Karolinska Institutet
Dorothea Buck - Technical University of Munich
Helmut Butzkueven - University of Melbourne
Stacy J Caillier - University of California, San Francisco
William Camu - Université de Montpellier, Institut des Neurosciences de Montpellier - INM
Wassila Carpentier - Université Sorbonne Nouvelle
Paola Cavalla - University of Turin
Elisabeth Celius - University of Oslo
Irène Coman
Giancarlo Comi
Lucia Corrado - Università degli Studi del Piemonte Orientale “Amedeo Avogadro”
Leentje Cosemans - KU Leuven
Isabelle Cournu-Rebeix - Institut du Cerveau
Bruce Cree - University of California, San Francisco
Daniele Cusi - University of Milan
Vincent Damotte - Institut du Cerveau
Gilles Defer - Université de Caen Normandie
Silvia Delgado - University of Miami
Panos Deloukas - Wellcome Sanger Institute
Alessia Di Sapio
Alexander T Dilthey - University of Oxford
Peter Donnelly - University of Oxford
Bénédicte Dubois - KU Leuven
Martin Duddy
Sarah Edkins
Irina Elovaara - Tampere University
Federica Esposito
Nikos Evangelou - Nottingham University Hospitals NHS Trust
Barnaby Fiddes - University of Cambridge
Judith Field - University of Melbourne
Andre Franke - Kiel University
Colin Freeman - University of Oxford
Irene Frohlich - Harvard University Press
Daniela Galimberti - University of Milan
Christian Gieger
Pierre-Antoine Gourraud - Epidémiologie et Analyses en Santé Publique : risques, maladies chroniques et handicap
Christiane Graetz - Johannes Gutenberg University Mainz
Andrew Graham - National Health Service
Verena Grummel - Technical University of Munich
Clara Guaschino
Athena Hadjixenofontos - University of Miami
Hakon Hakonarson - University of Pennsylvania
Christopher Halfpenny
Gillian Hall
Per Hall - Karolinska Institutet
Anders Hamsten - Karolinska Institutet
James Harley
Timothy Harrower
Clive Hawkins - University Hospitals of North Midlands NHS Trust
Garrett Hellenthal - University College London
Charles Hillier
Jeremy Hobart - University of Plymouth
Muni Hoshi - Technical University of Munich
Sarah Hunt
Maja Jagodic - Karolinska Institutet
Ilijas Jelčić - University of Zurich
Angela Jochim - Technical University of Munich
Brian Kendall
Allan Kermode - Murdoch University
Trevor Kilpatrick - University of Melbourne
Keijo Koivisto
Ioanna Konidari - University of Miami
Thomas Korn - Technical University of Munich
Helena Kronsbein - Technical University of Munich
Cordelia Langford
Malin Larsson - Linköping University
Mark Lathrop - McGill University
Christine Lebrun-Frenay - Centre Hospitalier Universitaire de Nice
Jeannette Lechner-Scott - University of Newcastle Australia
Michelle Lee - Harvard University Press
Maurizio Leone
Virpi Leppä - University of Helsinki
Giuseppe Liberatore
Benedicte Lie - University of Oslo
Christina Lill - Max Planck Society
Magdalena Lindén - Karolinska Institutet
Jenny Link - Karolinska Institutet
Felix Luessi - Johannes Gutenberg University Mainz
Jan Lycke - University of Gothenburg
Fabio Macciardi - University of Milan
Satu Männistö - Finnish Institute for Health and Welfare
Clara Manrique - University of Miami
Roland Martin
Vittorio Martinelli
Deborah Mason
Gordon Mazibrada - University Hospitals Birmingham NHS Foundation Trust
Cristin Mccabe - Broad Institute
Inger-Lise Mero
Julia Mescheriakova - Erasmus University Rotterdam
Loukas Moutsianas - University of Oxford
Kjell-Morten Myhr
Guy Nagels
Richard Nicholas
Petra Nilsson - Lund University
Fredrik Piehl - Karolinska Institutet
Matti Pirinen - University of Oxford
Siân Price
Hong Quach - University of California, Berkeley
Mauri Reunanen - University of Oulu
Wim Robberecht - KU Leuven
Neil Robertson - Cardiff University
Mariaemma Rodegher
David Rog
Marco Salvetti - Sapienza University of Rome
Nathalie Schnetz-Boutaud
Finn Sellebjerg - University of Copenhagen
Rebecca Selter - Technical University of Munich
Catherine Schaefer - Kaiser Permanente
Sandip Shaunak
Ling Shen - Kaiser Permanente
Simon Shields
Volker Siffrin - Johannes Gutenberg University Mainz
Mark Slee - Flinders University
Per Soelberg Sorensen
Melissa Sorosina
Mireia Sospedra - University of Zurich
Anne Spurkland - University of Oslo
Amy Strange - University of Oxford
Emilie Sundqvist - Karolinska Institutet
Vincent Thijs - KU Leuven
John Thorpe
Anna Ticca
Pentti Tienari - University of Helsinki
Cornelia M. van Duijn - Erasmus University Rotterdam
Elizabeth Visser - University of Aberdeen
Steve Vucic - University of Sydney
Helga Westerlind - Karolinska Institutet
James Wiley - University of Melbourne
Alastair Wilkins - University of Bristol
James Wilson - University of Edinburgh
Juliane Winkelmann - Technical University of Munich
John Zajicek - University of Plymouth
Eva Zindler - Johannes Gutenberg University Mainz
Jonathan L. Haines
Margaret Pericak-Vance - University of Miami
Adrian Ivinson - Harvard University Press
Graeme Stewart - University of Sydney
David A Hafler - Broad Institute
Stephen Hauser - University of California, San Francisco
Alastair Compston - University of Cambridge
Gil Mcvean - University of Oxford
Philip L de Jager - Broad Institute
Stephen Sawcer - University of Cambridge
Jacob Mccauley - University of Miami
Publication Details: Nature Genetics, Vol.45(11), pp.1353-1360
Identifiers: 9941209209311
Academic Unit: Institut des Neurosciences de Montpellier - INM
Language: English
Resource Type: Journal article
Local Fields: hal-02565210