Susceptibility Genes for Multiple Sclerosis Identified in a Gene-Based Genome-Wide Association Study.
10.3988/jcn.2015.11.4.311
- Author:
Xiang LIN
1
;
Fei Yan DENG
;
Xin LU
;
Shu Feng LEI
Author Information
1. Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu, People's Republic of China. leisf@suda.edu.cn
- Publication Type:Original Article
- Keywords:
multiple sclerosis;
gene-based GWAS;
gene expression;
human leukocyte antigen
- MeSH:
Central Nervous System;
Dataset;
Gene Expression;
Genome-Wide Association Study*;
Genotype;
Humans;
Leukocytes;
Major Histocompatibility Complex;
Molecular Biology;
Multiple Sclerosis*;
Myelin-Oligodendrocyte Glycoprotein;
Phenotype
- From:Journal of Clinical Neurology
2015;11(4):311-318
- CountryRepublic of Korea
- Language:English
-
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.
