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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.

SUBMITTER: International Multiple Sclerosis Genetics Consortium (IMSGC) 

PROVIDER: S-EPMC3832895 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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

Beecham Ashley H AH   Patsopoulos Nikolaos A NA   Xifara Dionysia K DK   Davis Mary F MF   Kemppinen Anu A   Cotsapas Chris C   Shah Tejas S TS   Spencer Chris C   Booth David D   Goris An A   Oturai Annette A   Saarela Janna J   Fontaine Bertrand B   Hemmer Bernhard B   Martin Claes C   Zipp Frauke F   D'Alfonso Sandra S   Martinelli-Boneschi Filippo F   Taylor Bruce B   Harbo Hanne F HF   Kockum Ingrid I   Hillert Jan J   Olsson Tomas T   Ban Maria M   Oksenberg Jorge R JR   Hintzen Rogier R   Barcellos Lisa F LF   Agliardi Cristina C   Alfredsson Lars L   Alizadeh Mehdi M   Anderson Carl C   Andrews Robert R   Søndergaard Helle Bach HB   Baker Amie A   Band Gavin G   Baranzini Sergio E SE   Barizzone Nadia N   Barrett Jeffrey J   Bellenguez Céline C   Bergamaschi Laura L   Bernardinelli Luisa L   Berthele Achim A   Biberacher Viola V   Binder Thomas M C TM   Blackburn Hannah H   Bomfim Izaura L IL   Brambilla Paola P   Broadley Simon S   Brochet Bruno B   Brundin Lou L   Buck Dorothea D   Butzkueven Helmut H   Caillier Stacy J SJ   Camu William W   Carpentier Wassila W   Cavalla Paola P   Celius Elisabeth G EG   Coman Irène I   Comi Giancarlo G   Corrado Lucia L   Cosemans Leentje L   Cournu-Rebeix Isabelle I   Cree Bruce A C BA   Cusi Daniele D   Damotte Vincent V   Defer Gilles G   Delgado Silvia R SR   Deloukas Panos P   di Sapio Alessia A   Dilthey Alexander T AT   Donnelly Peter P   Dubois Bénédicte B   Duddy Martin M   Edkins Sarah S   Elovaara Irina I   Esposito Federica F   Evangelou Nikos N   Fiddes Barnaby B   Field Judith J   Franke Andre A   Freeman Colin C   Frohlich Irene Y IY   Galimberti Daniela D   Gieger Christian C   Gourraud Pierre-Antoine PA   Graetz Christiane C   Graham Andrew A   Grummel Verena V   Guaschino Clara C   Hadjixenofontos Athena A   Hakonarson Hakon H   Halfpenny Christopher C   Hall Gillian G   Hall Per P   Hamsten Anders A   Harley James J   Harrower Timothy T   Hawkins Clive C   Hellenthal Garrett G   Hillier Charles C   Hobart Jeremy J   Hoshi Muni M   Hunt Sarah E SE   Jagodic Maja M   Jelčić Ilijas I   Jochim Angela A   Kendall Brian B   Kermode Allan A   Kilpatrick Trevor T   Koivisto Keijo K   Konidari Ioanna I   Korn Thomas T   Kronsbein Helena H   Langford Cordelia C   Larsson Malin M   Lathrop Mark M   Lebrun-Frenay Christine C   Lechner-Scott Jeannette J   Lee Michelle H MH   Leone Maurizio A MA   Leppä Virpi V   Liberatore Giuseppe G   Lie Benedicte A BA   Lill Christina M CM   Lindén Magdalena M   Link Jenny J   Luessi Felix F   Lycke Jan J   Macciardi Fabio F   Männistö Satu S   Manrique Clara P CP   Martin Roland R   Martinelli Vittorio V   Mason Deborah D   Mazibrada Gordon G   McCabe Cristin C   Mero Inger-Lise IL   Mescheriakova Julia J   Moutsianas Loukas L   Myhr Kjell-Morten KM   Nagels Guy G   Nicholas Richard R   Nilsson Petra P   Piehl Fredrik F   Pirinen Matti M   Price Siân E SE   Quach Hong H   Reunanen Mauri M   Robberecht Wim W   Robertson Neil P NP   Rodegher Mariaemma M   Rog David D   Salvetti Marco M   Schnetz-Boutaud Nathalie C NC   Sellebjerg Finn F   Selter Rebecca C RC   Schaefer Catherine C   Shaunak Sandip S   Shen Ling L   Shields Simon S   Siffrin Volker V   Slee Mark M   Sorensen Per Soelberg PS   Sorosina Melissa M   Sospedra Mireia M   Spurkland Anne A   Strange Amy A   Sundqvist Emilie E   Thijs Vincent V   Thorpe John J   Ticca Anna A   Tienari Pentti P   van Duijn Cornelia C   Visser Elizabeth M EM   Vucic Steve S   Westerlind Helga H   Wiley James S JS   Wilkins Alastair A   Wilson James F JF   Winkelmann Juliane J   Zajicek John J   Zindler Eva E   Haines Jonathan L JL   Pericak-Vance Margaret A MA   Ivinson Adrian J AJ   Stewart Graeme G   Hafler David D   Hauser Stephen L SL   Compston Alastair A   McVean Gil G   De Jager Philip P   Sawcer Stephen J SJ   McCauley Jacob L JL  

Nature genetics 20130929 11


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 susceptibi  ...[more]

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