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

Patsopoulos, N.A., de Bakker, P.I.W. and Kermode, A.G. (2011) Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci. Annals of Neurology, 70 (6). pp. 897-912.

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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.

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.

We meta-analyzed 2,529,394 unique SNPs in 5,545 cases and 12,153 controls. We identified 3 novel susceptibility alleles: rs170934T at 3p24.1 (odds ratio [OR], 1.17; p = 1.6 × 10−8) near EOMES, rs2150702G in the second intron of MLANA on chromosome 9p24.1 (OR, 1.16; p = 3.3 × 10−8), and rs6718520A 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 < 1 × 10−6, some of these loci have evidence of association in other inflammatory diseases (ie, IL12B, TAGAP, PLEK, and ZMIZ1).

Publication Type: Journal Article
Publisher: Wiley
Copyright: © 2011 American Neurological Association
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