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Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci

Journal article published in 2011 by Federica Esposito, Joachim Reischl, Bayer Pharma Ms Genetics Working Group, Stephan Lehr, David Bauer, Jürgen Heubach, Ludwig Kappos, Rupert Sandbrink, David Miller, Nikolaos A. Patsopoulos, Chris H. Polman, Christoph Pohl, Javier Montalbán, Gilles Edan, Mark S. Freedman and other authors.
This paper is available in a repository.
This paper is available in a repository.

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Abstract

OBJECTIVE: To perform a 1-stage meta-analysis of genome-wide association studies (GWAS) of multiple sclerosis (MS) susceptibility and to explore functional consequences of new susceptibility loci. METHODS: We synthesized 7 MS GWAS. Each data set was imputed using HapMap phase II, and a per single nucleotide polymorphism (SNP) meta-analysis was performed across the 7 data sets. We explored RNA expression data using a quantitative trait analysis in peripheral blood mononuclear cells (PBMCs) of 228 subjects with demyelinating disease. RESULTS: We meta-analyzed 2,529,394 unique SNPs in 5,545 cases and 12,153 controls. We identified 3 novel susceptibility alleles: rs170934(T) at 3p24.1 (odds ratio [OR], 1.17; p = 1.6 × 10(-8)) near EOMES, rs2150702(G) in the second intron of MLANA on chromosome 9p24.1 (OR, 1.16; p = 3.3 × 10(-8)), and rs6718520(A) in an intergenic region on chromosome 2p21, with THADA as the nearest flanking gene (OR, 1.17; p = 3.4 × 10(-8)). The 3 new loci do not have a strong cis effect on RNA expression in PBMCs. Ten other susceptibility loci had a suggestive p