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 DAlfonso; 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 Sondergaard; Amie Baker; Gavin Band; Sergio E. Baranzini; Nadia Barizzone; Jeffrey Barrett; Celine Bellenguez; Laura Bergamaschi; Luisa Bernardinelli; Achim Berthele; Viola Biberacher; Thomas M C. 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; Irene 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; Benedicte 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 Jelcic; 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 Leppa; Giuseppe Liberatore; Benedicte A. Lie; Christina M. Lill; Magdalena Linden; Jenny Link; Felix Luessi; Jan Lycke; Fabio Macciardi; Satu Mannisto; 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; Sian 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 F. 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; Wellcome Trust Case Control Consor

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 H. Beecham, Nikolaos A. Patsopoulos, Dionysia K. Xifara, Mary F. Davis, Anu Kemppinen, Chris Cotsapas, Tejas S. Shah, Chris Spencer, David Booth, An Goris, …

Nature genetics, Vol.45(11), pp.1353-+

01/11/2013

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

PMCID: PMC3832895

PMID: 24076602

Abstract

Engineering and Technology

TECHNOLOGY

Teknik och teknologier

TEKNIKVETENSKAP

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 andlt; 1.0 x 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 andlt; 5.0 x 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 H. Beecham - University of Miami
Nikolaos A. Patsopoulos - Brigham and Women's Hospital
Dionysia K. Xifara - University of Oxford
Mary F. Davis - Vanderbilt University
Anu Kemppinen - University of Cambridge
Chris Cotsapas - Broad Institute
Tejas S. Shah - Wellcome Sanger Institute
Chris Spencer - University of Oxford
David Booth - University of Sydney
An Goris - KU Leuven
Annette Oturai - Copenhagen University Hospital
Janna Saarela - University of Helsinki
Bertrand Fontaine - Université Paris Cité
Bernhard Hemmer - Technical University of Munich
Claes Martin - Danderyd Hospital, Sweden
Frauke Zipp - Johannes Gutenberg University of Mainz, Germany
Sandra DAlfonso - University of Piemonte Orientale, Italy
Filippo Martinelli-Boneschi - Ist Science San Raffaele, Italy
Bruce Taylor - University of Tasmania
Hanne F. Harbo - Oslo University Hospital
Ingrid Kockum - Karolinska Institutet
Jan Hillert - Karolinska Institutet
Tomas Olsson - Karolinska Institutet
Maria Ban - University of Cambridge
Jorge R. Oksenberg - University of Calif San Francisco, CA USA
Rogier Hintzen - Erasmus University, Netherlands
Lisa F Barcellos - University of Calif Berkeley, CA 94720 USA
Cristina Agliardi - IRCCS Santa Maria Nascente, Italy
Lars Alfredsson - Karolinska Institutet
Mehdi Alizadeh - University of Rennes
Carl Anderson - Wellcome Sanger Institute
Robert Andrews - Wellcome Sanger Institute
Helle Bach Sondergaard - Copenhagen University Hospital
Amie Baker - University of Cambridge
Gavin Band - University of Oxford
Sergio E. Baranzini - University of Calif San Francisco, CA USA
Nadia Barizzone - University of Piemonte Orientale, Italy
Jeffrey Barrett - Wellcome Sanger Institute
Celine Bellenguez - University of Oxford
Laura Bergamaschi - University of Piemonte Orientale, Italy
Luisa Bernardinelli - Massachusetts Rehabilitation Commission
Achim Berthele - Technical University of Munich
Viola Biberacher - Technical University of Munich
Thomas M C. Binder - University of Medical Centre Hamburg Eppendorf, Germany
Hannah Blackburn - Wellcome Sanger Institute
Izaura L. Bomfim - Karolinska Institutet
Paola Brambilla - Ist Science San Raffaele, Italy
Simon Broadley - Griffith University
Bruno Brochet - University of Bordeaux
Lou Brundin - Karolinska Institutet
Dorothea Buck - Technical University of Munich
Helmut Butzkueven - University of Melbourne
Stacy J. Caillier - University of Calif San Francisco, CA USA
William Camu - Centre Hospital University of Regional Montpellier, France
Wassila Carpentier - Université Paris Cité
Paola Cavalla - Azienda Osped Citta Salute and Science Torino, Italy
Elisabeth G. Celius - Oslo University Hospital
Irene Coman - Hop Avicenne, France
Giancarlo Comi - Ist Science San Raffaele, Italy
Lucia Corrado - University of Piemonte Orientale, Italy
Leentje Cosemans - KU Leuven
Isabelle Cournu-Rebeix - Université Paris Cité
Bruce A C. Cree - University of Calif San Francisco, CA USA
Daniele Cusi - University of Milan
Vincent Damotte - Université Paris Cité
Gilles Defer - CHU Caen, France
Silvia R. Delgado - University of Miami
Panos Deloukas - Wellcome Sanger Institute
Alessia di Sapio - University of San Luigi, Italy
Alexander T. Dilthey - University of Oxford
Peter Donnelly - University of Oxford
Benedicte Dubois - KU Leuven
Martin Duddy - Royal Victoria Infirm, England
Sarah Edkins - Wellcome Sanger Institute
Irina Elovaara - University of Tampere
Federica Esposito - Ist Science San Raffaele, Italy
Nikos Evangelou - University of Nottingham
Barnaby Fiddes - University of Cambridge
Judith Field - University of Melbourne
Andre Franke - University of Kiel, Germany
Colin Freeman - University of Oxford
Irene Y. Frohlich - Brigham and Women's Hospital
Daniela Galimberti - University of Milan
Christian Gieger - German Research Centre Environm Heatlh, Germany
Pierre-Antoine Gourraud - University of Calif San Francisco, CA USA
Christiane Graetz - Johannes Gutenberg University of Mainz, Germany
Andrew Graham - Ipswich Hospital National Health Serv NHS Trust, England
Verena Grummel - Technical University of Munich
Clara Guaschino - Ist Science San Raffaele, Italy
Athena Hadjixenofontos - University of Miami
Hakon Hakonarson - Childrens Hospital Philadelphia, PA USA
Christopher Halfpenny - Southampton Gen Hospital, England
Gillian Hall - Aberdeen Royal Infirm, Scotland
Per Hall - Karolinska Institutet
Anders Hamsten - Karolinska University Hospital
James Harley - Hull Royal Infirm, England
Timothy Harrower - Phillips Exeter Academy
Clive Hawkins - Keele University
Garrett Hellenthal - UCL, England
Charles Hillier - Poole Gen Hospital, England
Jeremy Hobart - University of Plymouth
Muni Hoshi - Technical University of Munich
Sarah E. Hunt - Wellcome Sanger Institute
Maja Jagodic - Karolinska Institutet
Ilijas Jelcic - University of Medical Centre Hamburg Eppendorf, Germany
Angela Jochim - Technical University of Munich
Brian Kendall - Leicester Royal Infirm, England
Allan Kermode - University of Western Australia
Trevor Kilpatrick - University of Melbourne
Keijo Koivisto - Seinajoki Central Hospital, Finland
Ioanna Konidari - University of Miami
Thomas Korn - Technical University of Munich
Helena Kronsbein - Technical University of Munich
Cordelia Langford - Wellcome Sanger Institute
Malin Larsson - Tekniska högskolan
Mark Lathrop - Centre Etud Polymorphisme Humain, France
Christine Lebrun-Frenay - CHRU Nice, France
Jeannette Lechner-Scott - University of Newcastle Australia
Michelle H. Lee - Brigham and Women's Hospital
Maurizio A. Leone - Osped Maggiore Novara, Italy
Virpi Leppa - University of Helsinki
Giuseppe Liberatore - Ist Science San Raffaele, Italy
Benedicte A. Lie - University of Oslo
Christina M. Lill - Johannes Gutenberg University of Mainz, Germany
Magdalena Linden - Karolinska Institutet
Jenny Link - Karolinska Institutet
Felix Luessi - Johannes Gutenberg University of Mainz, Germany
Jan Lycke - University of Gothenburg
Fabio Macciardi - University of Calif Irvine, CA USA
Satu Mannisto - National Institute Health and Welf, Finland
Clara P. Manrique - University of Miami
Roland Martin - University of Medical Centre Hamburg Eppendorf, Germany
Vittorio Martinelli - Ist Science San Raffaele, Italy
Deborah Mason - Canterbury Dist Health Board, New Zealand
Gordon Mazibrada - Queen Elizabeth Medical Centre, England
Cristin McCabe - Broad Institute
Inger-Lise Mero - Oslo University Hospital
Julia Mescheriakova - Erasmus University, Netherlands
Loukas Moutsianas - University of Oxford
Kjell-Morten Myhr - Haukeland Hospital, Norway
Guy Nagels - National Multiple Sclerosis Centre Melsbroek, Belgium
Richard Nicholas - Charing Cross Hospital
Petra Nilsson - Lund University
Fredrik Piehl - Karolinska Institutet
Matti Pirinen - University of Oxford
Sian E. Price - Royal Hallamshire Hospital
Hong Quach - University of Calif Berkeley, CA USA
Mauri Reunanen - University of Oulu
Wim Robberecht - Vesalius Research Centre, Belgium
Neil P. Robertson - Cardiff University
Mariaemma Rodegher - Ist Science San Raffaele, Italy
David Rog - Salford Royal NHS Fdn Trust, England
Marco Salvetti - University of Roma La Sapienza, Italy
Nathalie C. Schnetz-Boutaud - Vanderbilt University
Finn Sellebjerg - Copenhagen University Hospital
Rebecca C. Selter - Technical University of Munich
Catherine Schaefer - Kaiser Permanente
Sandip Shaunak - Royal Preston Hospital
Ling Shen - Kaiser Permanente
Simon Shields - Norfolk and Norwich University Hospital
Volker Siffrin - Johannes Gutenberg University of Mainz, Germany
Mark Slee - Flinders University
Per Soelberg Sorensen - Copenhagen University Hospital
Melissa Sorosina - Ist Science San Raffaele, Italy
Mireia Sospedra - University of Medical Centre Hamburg Eppendorf, Germany
Anne Spurkland - University of Oslo
Amy Strange - University of Oxford
Emilie Sundqvist - Karolinska Institutet
Vincent Thijs - Vesalius Research Centre, Belgium
John Thorpe - Peterborough City Hospital
Anna Ticca - San Francesco Hospital, Italy
Pentti Tienari - University of Helsinki
Cornelia van Duijn - Erasmus MC
Elizabeth M. Visser - University of Aberdeen
Steve Vucic - University of Sydney
Helga Westerlind - Karolinska Institutet
James S. Wiley - University of Melbourne
Alastair Wilkins - University of Bristol
James F. Wilson - University of Edinburgh
Juliane Winkelmann - Technical University of Munich
John Zajicek - University of Plymouth
Eva Zindler - Johannes Gutenberg University of Mainz, Germany
Jonathan L. Haines - Vanderbilt University
Margaret A. Pericak-Vance - University of Miami
Adrian J. Ivinson - Harvard University
Graeme Stewart - University of Sydney
David Hafler - Broad Institute
Stephen L. Hauser - University of Calif San Francisco, CA USA
Alastair Compston - University of Cambridge
Gil McVean - University of Oxford
Philip De Jager - Brigham and Women's Hospital
Stephen J. Sawcer - University of Cambridge
Jacob L. McCauley - University of Miami
Wellcome Trust Case Control Consor
Publication Details: Nature genetics, Vol.45(11), pp.1353-+
Identifiers: 9934453008331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article