Susceptibility Genes for Multiple Sclerosis Identified in a Gene-Based Genome-Wide Association Study.
Susceptibility Genes for Multiple Sclerosis Identified in a Gene-Based Genome-Wide Association Study.
复制标题
基于基因的全基因组关联研究鉴定出多发性硬化症的易感基因
DOI：
10.3988/jcn.2015.11.4.311
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发表时间：
2015-10
期刊：
影响因子：
--
通讯作者：
Lei SF
中科院分区：
文献类型：
--
作者：
Lin X;Deng FY;Lu X;Lei SF
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<1.40×10-4). 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.
