Journal article
Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci
Annals of Neurology, Vol.70(6), pp.897-912
2011
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 = 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).
Details
- Title
- Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci
- Authors/Creators
- N.A. Patsopoulos (Author/Creator) - Massachusetts Institute of TechnologyP.I.W. de Bakker (Author/Creator)A.G. Kermode (Author/Creator)
- Publication Details
- Annals of Neurology, Vol.70(6), pp.897-912
- Publisher
- Wiley
- Identifiers
- 991005544870607891
- Copyright
- © 2011 American Neurological Association
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.203 Neuromuscular Disorders
- 1.203.147 Multiple Sclerosis
- Web Of Science research areas
- Clinical Neurology
- Neurosciences
- ESI research areas
- Neuroscience & Behavior