title: Susceptibility Genes for Multiple Sclerosis Identified in a Gene-Based Genome-Wide Association Study.
abstract: OBJECTIVE
  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.
authors: Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu, People's Republic of China.|Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou, Jiangsu, People's Republic of China.|Department of Tuberculosis Control, Ningbo Municipal Center for Disease Control & Prevention, Ningbo, Zhejiang, People's Republic of China.
authors: Xiang
authors: X
authors: Lin
authors: Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu, People's Republic of China.|Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou, Jiangsu, People's Republic of China.
authors: Fei Yan
authors: FY
authors: Deng
authors: Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu, People's Republic of China.|Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou, Jiangsu, People's Republic of China.
authors: Xin
authors: X
authors: Lu
authors: Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou, Jiangsu, People's Republic of China.|Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu, People's Republic of China. leisf@suda.edu.cn.
authors: Shu Feng
authors: SF
authors: Lei
keywords: gene expression; gene-based GWAS; human leukocyte antigen; multiple sclerosis