Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis
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Résumé
The International Multiple Sclerosis Genetics Consortium reports the discovery of 48 new susceptibility variants for multiple sclerosis through targeted follow-up of immune-related loci. They also report fine mapping of association signals at established susceptibility loci and provide insights into the immune system processes underlying this disease. 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.
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La notice
- Revue
- Nature Genetics
- Thématique
- Multiple Sclerosis Research Studies
- Domaine
- Medicine
- Établissements canadiens
- McGill University and Génome Québec Innovation CentreMcGill University
- Organismes subventionnaires
- National Center for Research ResourcesNational Cancer InstituteNational Institute of Allergy and Infectious DiseasesMedical Research CouncilNational Institutes of HealthNational Institute of Environmental Health SciencesInstitut National de la Santé et de la Recherche MédicaleKarolinska InstitutetHjärt-LungfondenVetenskapsrådetCrohn's and Colitis UKWellcome TrustInfrastructures en Biologie Santé et AgronomieMultiple Sclerosis SocietyKnut och Alice Wallenbergs StiftelseStockholms Läns LandstingNational Institute of Neurological Disorders and StrokeNational Institute of General Medical SciencesNational Institute for Health and Care Research
- Mots-clés
- Multiple sclerosisGenome-wide association studyBiologyGenotypingGeneticsMajor histocompatibility complexGenetic association1000 Genomes ProjectSingle-nucleotide polymorphismComputational biologyGenotypeImmune systemGeneImmunology
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