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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
Nat Genet 2013; 45(11):1353-60NGen

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.

Authors+Show Affiliations

1] John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida, USA. 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Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24076602

Citation

International Multiple Sclerosis Genetics Consortium (IMSGC), et al. "Analysis of Immune-related Loci Identifies 48 New Susceptibility Variants for Multiple Sclerosis." Nature Genetics, vol. 45, no. 11, 2013, pp. 1353-60.
International Multiple Sclerosis Genetics Consortium (IMSGC), Beecham AH, Patsopoulos NA, et al. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet. 2013;45(11):1353-60.
Beecham, A. H., Patsopoulos, N. A., Xifara, D. K., Davis, M. F., Kemppinen, A., Cotsapas, C., ... McCauley, J. L. (2013). Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nature Genetics, 45(11), pp. 1353-60. doi:10.1038/ng.2770.
International Multiple Sclerosis Genetics Consortium (IMSGC), et al. Analysis of Immune-related Loci Identifies 48 New Susceptibility Variants for Multiple Sclerosis. Nat Genet. 2013;45(11):1353-60. PubMed PMID: 24076602.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. AU - ,, 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 - ,, AU - ,, 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 - Jelčić,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, Y1 - 2013/09/29/ PY - 2013/04/24/received PY - 2013/09/03/accepted PY - 2013/10/1/entrez PY - 2013/10/1/pubmed PY - 2014/1/9/medline SP - 1353 EP - 60 JF - Nature genetics JO - Nat. Genet. VL - 45 IS - 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. SN - 1546-1718 UR - https://www.unboundmedicine.com/medline/citation/24076602/full_citation L2 - http://dx.doi.org/10.1038/ng.2770 DB - PRIME DP - Unbound Medicine ER -