Tags

Type your tag names separated by a space and hit enter

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.

Links

  • PMC Free PDF
  • PMC Free Full Text
  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    1] John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida, USA. [2].

    , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,

    Source

    Nature genetics 45:11 2013 Nov pg 1353-60

    MeSH

    Chromosome Mapping
    European Continental Ancestry Group
    Gene Frequency
    Genetic Loci
    Genetic Predisposition to Disease
    Genetic Variation
    Genome-Wide Association Study
    Genotype
    Humans
    Multiple Sclerosis
    Polymorphism, Single Nucleotide

    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 -