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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.

Original publication

DOI

10.1038/ng.2770

Type

Journal article

Journal

Nature genetics

Publication Date

11/2013

Volume

45

Pages

1353 - 1360

Addresses

1] John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida, USA. [2].

Keywords

International Multiple Sclerosis Genetics Consortium (IMSGC), Wellcome Trust Case Control Consortium 2 (WTCCC2), International IBD Genetics Consortium (IIBDGC), Humans, Multiple Sclerosis, Genetic Predisposition to Disease, Chromosome Mapping, Gene Frequency, Genotype, Polymorphism, Single Nucleotide, European Continental Ancestry Group, Genetic Variation, Genome-Wide Association Study, Genetic Loci