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Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility

2019· article· en· 1,417 citations· W2981477552 on OpenAlex· 10.1126/science.aav7188

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Abstract

We analyzed genetic data of 47,429 multiple sclerosis (MS) and 68,374 control subjects and established 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 variants within the extended MHC. We used an ensemble of methods to prioritize 551 putative 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 observed enrichment for MS genes in these brain-resident immune cells, suggesting that these may have a role in targeting an autoimmune process to the central nervous system, although MS is most likely initially triggered by perturbation of peripheral immune responses.

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The record

Venue
Science
Topic
T-cell and B-cell Immunology
Field
Immunology and Microbiology
Canadian institutions
Funders
National Institute of Environmental Health SciencesNational Institute of Neurological Disorders and StrokeNational Institute of Allergy and Infectious DiseasesNIHR Oxford Biomedical Research CentreMenzies Centre for Australian Studies, King's College London, University of LondonMedical Research CouncilNIHR BioResourceLeonard M. Miller School of MedicineNational Institutes of HealthSorbonne UniversitéUK Dementia Research InstituteNational Institute on AgingMenzies Institute for Medical ResearchFundació Institut de Recerca Hospital Universitari Vall d’HebronNovo Nordisk Foundation Center for Basic Metabolic ResearchUniversité de LyonUniversité de NantesFaculty of Health and Medical Sciences, University of Western AustraliaUniversità degli Studi di TorinoUniversidad Pública de NavarraUniversité Claude Bernard Lyon 1H. Lundbeck A/SHospital for Sick ChildrenTechnische Universität MünchenNorges ForskningsrådRigshospitaletKing's College LondonCentre National de la Recherche ScientifiqueVetenskapsrådetKnut och Alice Wallenbergs StiftelseCambridge University HospitalsKU LeuvenFonds Wetenschappelijk OnderzoekYale UniversityKarolinska InstitutetAFA FörsäkringBundesministerium für Bildung und ForschungInstitut National de la Santé et de la Recherche MédicaleUniversità degli Studi del Piemonte OrientaleBiogenAgence Nationale de la RechercheNational Institute of General Medical SciencesJohannes Gutenberg-Universität MainzUniversity of TasmaniaStrategiske ForskningsrådUniversity of CambridgeChildren's Hospital of PhiladelphiaMultiple Sclerosis SocietyVlaamse regeringNational Institute for Health and Care ResearchKeele UniversityUniversité de LilleNovo NordiskFondation pour l'Aide à la Recherche sur la Sclérose en PlaquesUniversity of PennsylvaniaPerelman School of Medicine, University of PennsylvaniaVertex PharmaceuticalsLundbeckfondenUniversity College LondonWellcome TrustUniversitätsspital ZürichVanderbilt UniversityWestmead Millennium Institute for Medical ResearchMcGill UniversityScleroseforeningenHospices Civils de LyonUniversitetet i OsloJohns Hopkins UniversityForskningsrådet om Hälsa, Arbetsliv och VälfärdBroad InstituteEuropean CommissionMenzies Research Institute TasmaniaUniversità degli Studi di MilanoUniversity of MiamiVanderbilt University Medical CenterHelsingin YliopistoDet Sundhedsvidenskabelige Fakultet, Københavns UniversitetHarvard UniversityUniversity of OxfordKaiser PermanenteNational Multiple Sclerosis SocietyNovo Nordisk FondenCase Western Reserve UniversityHarvard NeuroDiscovery Center
Keywords
Multiple sclerosisImmune systemMajor histocompatibility complexMicrogliaBiologyGeneImmunologyInnate immune systemGeneticsInflammation
Has abstract in OpenAlex
yes