Susceptibility Genes for Multiple Sclerosis Identified in a Gene-Based Genome-Wide Association Study
Journal of Clinical Neurology
;
: 311-318, 2015.
Article
in English
| WPRIM
| ID: wpr-188623
ABSTRACT
BACKGROUND AND PURPOSE:
Multiple sclerosis (MS) is a demyelinating and inflammatory disease of the central nervous system. The aim of this study was to identify more genes associated with MS.METHODS:
Based on the publicly available data of the single-nucleotide polymorphism-based genome-wide association study (GWAS) from the database of Genotypes and Phenotypes, we conducted a powerful gene-based GWAS in an initial sample with 931 family trios, and a replication study sample with 978 cases and 883 controls. For interesting genes, gene expression in MS-related cells between MS cases and controls was examined by using publicly available datasets.RESULTS:
A total of 58 genes was identified, including 20 "novel" genes significantly associated with MS (p<1.40x10(-4)). In the replication study, 44 of the 58 identified genes had been genotyped and 35 replicated the association. In the gene-expression study, 21 of the 58 identified genes exhibited differential expressions in MS-related cells. Thus, 15 novel genes were supported by replicated association and/or differential expression. In particular, four of the novel genes, those encoding myelin oligodendrocyte glycoprotein (MOG), coiled-coil alpha-helical rod protein 1 (CCHCR1), human leukocyte antigen complex group 22 (HCG22), and major histocompatibility complex, class II, DM alpha (HLA-DMA), were supported by the evidence of both.CONCLUSIONS:
The results of this study emphasize the high power of gene-based GWAS in detecting the susceptibility genes of MS. The novel genes identified herein may provide new insights into the molecular genetic mechanisms underlying MS.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Phenotype
/
Gene Expression
/
Central Nervous System
/
Genome-Wide Association Study
/
Myelin-Oligodendrocyte Glycoprotein
/
Dataset
/
Genotype
/
Leukocytes
/
Major Histocompatibility Complex
/
Molecular Biology
Limits:
Humans
Language:
English
Journal:
Journal of Clinical Neurology
Year:
2015
Type:
Article
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