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

Citation

Beechham, AH and Patsopoulos, NA and Xifara, DK and Davis, MF and Kemppinen, A and Cotsapas, C and Shah, TS and Spencer, C and Booth, D and Goris, A and Oturai, A and Saarela, J and Fontaine, B and Hemmer, B and Martin, C and Zipp, F and D'Alfonso, S and Martinelli-Boneschi, F and Taylor, B and Harbo, HF and Kockum, I and Hillert, J and Olsson, T and Ban, M and Oksenberg, JR and Hintzen, R and Barcellos, LF and Agliardi, C and Alfredsson, L and Alizadeh, M and Anderson, C and Andrews, R and Sondergaard, HB and Baker, A and Band, G and Baranzini, SE and Barizzone, N and Barrett, J and Bellenguez, C and Bergamaschi, L and Bernardinelli, L and Berthele, A and Biberacher, V and Binder, TM and Blackburn, H and Bomfim, IL and Brambilla, P and Broadley, S and Brochet, B and Brundin, L and Buck, D and Butzkueven, H and Caillier, SJ and Camu, W and Carpentier, W and Cavalla, P and Celius, EG and Coman, I and Comi, G and Corrado, L and Cosemans, L and Cournu-Rebeix, I and Cree, BA and Cusi, D and Damotte, V and Defer, G and Delgado, SR and Deloukas, P and di Sapio, A and Dilthey, AT and Donnelly, P and Dubois, B and Duddy, M and Edkins, S and Elovaara, I and Esposito, F and Evangelou, N and Fiddes, B and Field, J and Franke, A and Freeman, C and Frohlich, IY and Galimberti, D and Gieger, C and Gourraud, PA and Graetz, C and Graham, A and Grummel, V and Guaschino, C and Hadjixenofontos, A and Hakonarson, H and Halfpenny, C and Hall, G and Hall, P and Hamsten, A and Harley, J and Harrower, T and Hawkins, C and Hellenthal, G and Hillier, C and Hobart, J and Hoshi, M and Hunt, SE and Jagodic, M and Jelcic, I and Jochim, A and Kendall, B and Kermode, A and Kilpatrick, T and Koivisto, K and Konidari, I and Korn, T and Kronsbein, H and Langford, C and Larsson, M and Lathrop, M and Lebrun-Frenay, C and Lechner-Scott, J and Lee, MH and Leone, MA and Lepp, V and Liberatore, G and Lie, BA and Lill, CM and Linden, M and Link, J and Luessi, F and Lycke, J and Macciardi, F and Mannisto, S and Manrique, CP and Martin, R and Martinelli, V and Mason, D and Mazibrada, G and McCabe, C and Mero, IL and Mescheriakova, J and Moutsianas, L and Myhr, KM and Nagels, G and Nicholas, R and Nilsson, P and Piehl, F and Pirinen, M and Price, SE and Quach, H and Reunanen, M and Robberecht, W and Robertson, NP and Rodegher, M and Rog, D and Salvetti, M and Schnetz-Boutaud, NC and Sellebjerg, F and Selter, RC and Schaefer, C and Shaunak, S and Shen, L and Shields, S and Siffrin, V and Slee, M and Sorensen, PS and Sorosina, M and Sospedra, M and Spurkland, A and Strange, A and Sundqvist, E and Thijs, V and Thorpe, J and Ticca, A and Tienari, P and van Duijn, C and Visser, EM and Vucic, S and Westerlind, H and Wiley, JS and Wilkins, A and Wilson, JF and Winkelmann, J and Zajicek, J and Zindler, E and Haines, JL and Pericak-Vance, MA and Ivinson, AJ and Stewart, G and Hafler, D and Hauser, SL and Compston, A and McVean, G and De Jager, P and Sawcer, SJ and McCauley, JL, Wellcome Trust Case Control Consortium 2 (WTCCC2); International IBD Genetics Consortium (IIBDGC), Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis, Nature Genetics, 45, (11) pp. 1353-1360. ISSN 1061-4036 (2013) [Refereed Article]

Copyright Statement

Copyright 2013 Macmillan Publishers

DOI: doi:10.1038/ng.2770

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.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Central Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Taylor, B (Professor Bruce Taylor)
ID Code:88179
Year Published:2013
Web of Science® Times Cited:427
Deposited By:Menzies Institute for Medical Research
Deposited On:2014-01-16
Last Modified:2015-03-02
Downloads:0

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