6533b839fe1ef96bd12a5aca
RESEARCH PRODUCT
The Multiple Sclerosis Genomic Map: Role of peripheral immune cells and resident microglia in susceptibility
Ashley BeechamDavid A. HaflerColombe JUblick KStephen SawcerMarcus C. S. LeeAdam SantanielloAn GorisFrank SeiboldXavier MontalbanG. ComiChristiane GasperiSandra D'alfonsoFederica EspositoLaurent Peyrin-birouletFrauke ZippIoanna KonidariElisabeth Gulowsen CeliusAchim BertheleAmoroso ARogier Q. HintzenJohan Van LimbergenMarieme DembeleFredrik KarpeZhang WRobbins AMoiola LAnnette Bang OturaiCristin MccabeFilippo Martinelli-boneschiM LindénKeith R EdwardsHanne F. HarboZuccalà MMarc LémannFelix LuessiNoriko IsobeNadia BarizzoneRenata D'incàCroft AIoannis S. VlachosFrohlich IMartinelliDaniela GalimbertiEfthimios DardiotisLisa F. BarcellosBrendan T. KeenanMaja JagodicFerdinando ClarelliBénédicte DuboisNicholas A. KennedyLohith MadireddyGrant W. MontgomeryTommy OlssonPhil De JagerLo APeter A. CalabresiBrandes AChris CotsapasBakker PdSteffan D. BosChristina M. LillKarban AThoerner LwTojo JamesWong GHarald PeetersM.-m. HoshiRoberts RFredrik PiehlLars AlfredssonGiorgos M. HadjigeorgiouBertrand FontaineMelissa SorosinaBenedetti MMaria BanJorge R. OksenbergHoward L. WeinerIngrid KockumMireia SospedraTaylor KmHenrik UllumIzaura Lima BomfimStronati LMolyneux PReplogle JStacy J. CaillierZhang HTill F. M. AndlauerMargaret A. Pericak-vanceJan HillertLuisa BernardinelliTaibo LiHelle Bach SøndergaardIlijas JelcicNikolaos A. PatsopoulosSilvia DelgadoCathy SchaeferThomas KornLaura PiccioMark MühlauDeborah D. ProctorB. HemmerElizabeth M. BradshawHysi PMegan C NevilleMary F. DavisDorlan J. KimbroughJyoti KhadakeJean-pierre HugotJean-pierre HugotDavid Gomez-cabreroMurray L. BarclayAnne H. CrossKasper LageStephen L. HauserA CompstonZimmer AIvinson AAnne SpurklandJonas HalfvarsonCharles C. WhiteBiberacherZarzycki OKathryn C. FitzgeraldFinn SellebjergEllis PatrickAndrea ZauliBruce V. TaylorMaurizio LeoneGenevieve LachanceMarta OlahB. CreeManuel ComabellaArie LevineDomizia VecchioMathias ChamaillardMark LathropClara GuaschinoRoland MartinHanigan KPierre-antoine F. D. GourraudMaria CimpeanJonathan L. HainesDorothea BuckMarco SalvettiPer Soelberg SørensenNoel LgMitja MitrovicGraeme J. StewartBenjamin KnierEllen LathiCottone MLaura FerrèWinn PDuijn CvMonica MillaTune H. PersI. OikonomouAn DDavid R. BoothRebeix IcClara P. ManriqueMassey DEvelyn Ng SmTörkvist LDaniele CusiShoostari PVatn MhPaola CavallaSilvia SantoroGossum AvSeema KalraPaul RutgeertsClive HawkinsSandra VukusikKhan MaHakon HakonarsonPaul HendersonPaul HendersonChristiane GraetzJulia Y MescheriakovaJean-françois RahierPanteliadis ICristina AgliardiGrummelJacob L. MccauleyAmie BakerJanna SaarelaSergio E. BaranziniJ W ThorpeDamottesubject
0303 health sciencesMicrogliaMultiple sclerosisCentral nervous systemBiologymedicine.diseaseMajor histocompatibility complex03 medical and health sciences0302 clinical medicineImmune systemmedicine.anatomical_structureAutoimmune ProcessImmunologymedicinebiology.proteinGene030217 neurology & neurosurgeryX chromosome030304 developmental biologydescription
Abstract:We assembled and analyzed genetic data of 47,351 multiple sclerosis (MS) subjects and 68,284 control subjects and establish a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 independent associations within the extended MHC. We used an ensemble of methods to prioritize up to 551 potentially associated MS susceptibility genes, that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we do find enrichment for MS genes in these brain - resident immune cells. Thus, while MS is most likely initially triggered by perturbation of peripheral immune responses the functional responses of microglia and other brain cells are also altered and may have a role in targeting an autoimmune process to the central nervous system.One Sentence Summary:We report a detailed genetic and genomic map of multiple sclerosis, and describe the role of putatively affected genes in the peripheral immune system and brain resident microglia.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-07-13 |