6533b86ffe1ef96bd12cd435
RESEARCH PRODUCT
Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
Bénédicte DuboisLucia CorradoDeborah F. MasonAllan G. KermodeAllan G. KermodePentti J. TienariAnnette Bang OturaiCharles HillierAdrian J. IvinsonStephen L. HauserAshley BeechamJeannette Lechner-scottVincent ThijsJonathan L. HainesSarah EdkinsAlexander T. DiltheyDaniele CusiGuy NagelsDavid A. HaflerDavid A. HaflerMark SleePetra NilssonJames S. WileyLou BrundinAmy StrangeElizabeth VisserMireia SospedraMireia SospedraAthena HadjixenofontosSergio E. BaranziniJenny LinkRobert AndrewsViola BiberacherHelle Bach SøndergaardVittorio MartinelliTomas OlssonGillian L HallStephen SawcerStacy J. CaillierPer Soelberg SørensenCéline BellenguezCornelia M. Van DuijnFrauke ZippNikolaos A. PatsopoulosNikolaos A. PatsopoulosCristin MccabeColin FreemanSimon BroadleyLuisa BernardinelliMargaret A. Pericak-vanceJan HillertWassila CarpentierSandip ShaunakAnne SpurklandBarnaby FiddesJudith FieldJan LyckeChristina M. LillChristina M. LillFederica EspositoIoanna KonidariElisabeth Gulowsen CeliusChristian GiegerHelmut ButzkuevenHelmut ButzkuevenLing ShenJames F. WilsonMagdalena LindénTejas S. ShahAmie BakerDionysia K. XifaraHong QuachLaura BergamaschiRogier Q. HintzenJacob L. MccauleyJanna SaarelaJ W ThorpeChristine Lebrun-frenayFelix LuessiSandra D'alfonsoB. E. KendallHelga WesterlindGiancarlo ComiNathalie Schnetz-boutaudPaola BrambillaChris CotsapasChris CotsapasAnders HamstenWilliam CamuAchim BertheleKjell-morten MyhrClive HawkinsRichard NicholasJames HarleyCarl A. AndersonKeijo KoivistoIrene ComanNeil RobertsonHakon HakonarsonFinn SellebjergFredrik Piehl Di Sapio AlessiaLoukas MoutsianasMehdi AlizadehLars AlfredssonCatherine SchaeferDavid RogVirpi LeppaC. MartinBruce A.c. CreeChristopher HalfpennyIrina ElovaaraFilippo Martinelli-boneschiCordelia LangfordHanne F. HarboWim RobberechtIsabelle Cournu-rebeixSteve VucicIzaura Lima BomfimIrene Y. FrohlichMichelle LeeBertrand FontaineBernhard HemmerEva ZindlerChris C. A. SpencerMalin LarssonSimon ShieldsIlijas JelcicIlijas JelcicJuliane WinkelmannJorge R. OksenbergAlastair WilkinsSilvia DelgadoVolker SiffrinHelena C. KronsbeinBruno BrochetPanos DeloukasDaniela GalimbertiNikos EvangelouRebecca C. SelterMaja JagodicMartin DuddyTimothy HarrowerPer HallNadia BarizzoneSiân PriceMatti PirinenPierre-antoine GourraudThomas M.c. BinderLiberatore GiuseppeMark LathropMark LathropM.-m. HoshiGarrett HellenthalMelissa SorosinaThomas KornClara GuaschinoRoland MartinRoland MartinJeremy HobartMarco SalvettiPeter DonnellyIngrid KockumAn GorisAlastair CompstonMariaemma RodegherDorothea BuckClara P. ManriqueChristiane GraetzBenedicte A. LieTrevor J. KilpatrickAndrew GrahamAnu KemppinenMaria BanGil McveanJohn ZajicekHannah BlackburnMary F. DavisEmilie SundqvistBruce V. TaylorMaurizio LeoneLisa F. BarcellosLisa F. BarcellosLisa F. BarcellosFabio MacciardiFabio MacciardiGilles DeferVincent DamotteSatu MännistöGraeme J. StewartGordon MazibradaInger Lise MeroAndre FrankePhilip L. De JagerPhilip L. De JagerVerena GrummelMauri ReunanenDavid R. BoothAnna TiccaAngela JochimLeentje CosemansJulia Y MescheriakovaCristina AgliardiPaola CavallaJeffrey C. BarrettSarah E. HuntGavin Bandsubject
Multiple SclerosisGenotype[SDV]Life Sciences [q-bio]European Continental Ancestry GroupGenome-wide association studyCLEC16ABiologymultiple sclerosisMajor histocompatibility complexPolymorphism Single NucleotideArticleWhite People03 medical and health sciences0302 clinical medicineResearch Support N.I.H. ExtramuralGene FrequencyPolymorphism (computer science)Journal ArticleGeneticsmedicineHumansGenetic Predisposition to DiseaseAlleleGenotypingAllele frequency030304 developmental biologyGenetics0303 health sciencesResearch Support Non-U.S. Gov'tMultiple sclerosisChromosome MappingGenetic Variationmedicine.disease3. Good healthGenetic Locibiology.protein030217 neurology & neurosurgery[SDV.MHEP]Life Sciences [q-bio]/Human health and pathologyGenome-Wide Association Studydescription
International audience; 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2013-11-01 |