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.

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Affiliated Institutions

• KU Leuven BE
• University of California, Berkeley US
• University of Milan IT
• Michigan Technological University US
• The University of Melbourne AU
• University Hospitals of North Midlands NHS Trust GB
• University of Cambridge GB
• Kaiser Permanente US
• Sorbonne Université FR
• Yale University US
• Monash University AU
• Medical Research Council GB
• University College London GB
• Universität Hamburg DE
• Université de Caen Normandie FR
• Università degli Studi del Piemonte Orientale “Amedeo Avogadro” IT
• University of Oxford GB
• University of Pennsylvania US
• University of Turin IT
• Broad Institute US
• University of Oslo
• National Health Service GB
• Keele University GB
• Harvard University Press US
• University of Copenhagen DK
• Technical University of Munich DE
• Karolinska Institutet SE
• Erasmus University Rotterdam NL
• Tampere University FI
• University of Miami US
• Université de Rennes FR
• QB3 US
• Christian-Albrechts-Universität zu Kiel DE
• Nottingham University Hospitals NHS Trust GB
• Institute for Neurosciences of Montpellier FR
• Philadelphia University US
• Université de Bordeaux FR
• Johannes Gutenberg University Mainz DE
• University of Helsinki FI
• Wellcome Sanger Institute GB
• The University of Sydney AU
• Griffith University AU
• Institut du Cerveau FR
• University of California, San Francisco US
• University of Tasmania AU

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