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

Patsopoulos, Nikolaos A., de Bakker, Paul I., Griffiths, Lyn R., & Brown, Matthew A. (2011) Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci. Annals of Neurology, 70(6), pp. 897-912.

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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: rs170934T at 3p24.1 (odds ratio [OR], 1.17; p ¼ 1.6 � 10�8) near EOMES, rs2150702G in the second intron of MLANA on chromosome 9p24.1 (OR, 1.16; p ¼ 3.3 � 10�8), and rs6718520A in an intergenic region on chromosome 2p21, with THADA as the nearest flanking gene (OR, 1.17; p ¼ 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). Interpretation: We have performed a meta-analysis of GWAS in MS that more than doubles the size of previous gene discovery efforts and highlights 3 novel MS susceptibility loci. These and additional loci with suggestive evidence of association are excellent candidates for further investigations to refine and validate their role in the genetic architecture of MS.

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ID Code: 62548
Item Type: Journal Article
Refereed: Yes
DOI: 10.1002/ana.22609
ISSN: 03645134
Divisions: Current > Schools > School of Biomedical Sciences
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2011 John Wiley & Sons, Inc.
Deposited On: 16 Sep 2013 02:28
Last Modified: 23 Sep 2015 05:39

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