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

Patsopoulos, Nikolaos A., Bayer Pharma MS Genetics Working Group, Steering Committee of Studies Evaluating IFNβ-1b, Steering Committee of a CCR1-Antagonist, ANZgene Consortium, GeneMSA, International Multiple Sclerosis Genetics Consortium, de Bakker, Paul I. W., Brown, Matthew A. and Pender, Michael P. (2011) Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci. Annals of Neurology, 70 6: 897-912. doi:10.1002/ana.22609

Author Patsopoulos, Nikolaos A.
Bayer Pharma MS Genetics Working Group
Steering Committee of Studies Evaluating IFNβ-1b
Steering Committee of a CCR1-Antagonist
ANZgene Consortium
International Multiple Sclerosis Genetics Consortium
de Bakker, Paul I. W.
Brown, Matthew A.
Pender, Michael P.
Title Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci
Journal name Annals of Neurology   Check publisher's open access policy
ISSN 0364-5134
Publication date 2011-12
Sub-type Article (original research)
DOI 10.1002/ana.22609
Volume 70
Issue 6
Start page 897
End page 912
Total pages 16
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Collection year 2012
Language eng
Formatted abstract
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: 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 < 1 × 10 -6, some of these loci have evidence of association in other inflammatory diseases (ie, IL12B, TAGAP, PLEK, and ZMIZ1).

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.
Keyword Coronary-Artery-Disease
Association Analysis
Genotype Imputation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article first published online: 21 December 2011.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Medicine Publications
UQ Diamantina Institute Publications
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