Limits...
Susceptibility Genes for Multiple Sclerosis Identified in a Gene-Based Genome-Wide Association Study.

Lin X, Deng FY, Lu X, Lei SF - J Clin Neurol (2015)

Bottom Line: The aim of this study was to identify more genes associated with MS.A total of 58 genes was identified, including 20 "novel" genes significantly associated with MS (p<1.40×10⁻⁴).The results of this study emphasize the high power of gene-based GWAS in detecting the susceptibility genes of MS.

View Article: PubMed Central - PubMed

Affiliation: Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu, People's Republic of China.

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<1.40×10⁻⁴). 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.

No MeSH data available.


Related in: MedlinePlus

Protein-protein interactions between MS-associated genes. Only the connected genes are shown. The novel genes are labeled in red. Different line colors represent the types of evidence for the association. HLA class I cluster: major histocompatibility complex, class I, A (HLA-A), Major histocompatibility complex, class I, C (HLA-C), and major histocompatibility complex, class I, F (HLA-F); HLA class II cluster: major histocompatibility complex, class II, DQ alpha 1 (HLA-DQA1), major histocompatibility complex, class II, DQ alpha 2 (HLA-DQA2), major histocompatibility complex, class II, DQ beta 2 (HLA-DQB2), major histocompatibility complex, class II, DR alha (HLA-DRA), major histocompatibility complex, class II, DO beta (HLA-DOB), major histocompatibility complex, class II, DM alpha (HLA-DMA), and major histocompatibility complex, class II, DM beta (HLA-DMB). HLA: human leukocyte antigen, MS: Multiple sclerosis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4596110&req=5

Figure 3: Protein-protein interactions between MS-associated genes. Only the connected genes are shown. The novel genes are labeled in red. Different line colors represent the types of evidence for the association. HLA class I cluster: major histocompatibility complex, class I, A (HLA-A), Major histocompatibility complex, class I, C (HLA-C), and major histocompatibility complex, class I, F (HLA-F); HLA class II cluster: major histocompatibility complex, class II, DQ alpha 1 (HLA-DQA1), major histocompatibility complex, class II, DQ alpha 2 (HLA-DQA2), major histocompatibility complex, class II, DQ beta 2 (HLA-DQB2), major histocompatibility complex, class II, DR alha (HLA-DRA), major histocompatibility complex, class II, DO beta (HLA-DOB), major histocompatibility complex, class II, DM alpha (HLA-DMA), and major histocompatibility complex, class II, DM beta (HLA-DMB). HLA: human leukocyte antigen, MS: Multiple sclerosis.

Mentions: The 58 identified MS-associated genes were retrieved from the STRING database. Only 36 genes, including 10 novel genes, were annotated in this database. The genes at the HLA regions were clearly enriched into two clusters: HLA class I and II clusters (Fig. 3). Two novel genes, those encoding major histocompatibility complex, class, I, A (HLA-A) and major histocompatibility complex, class II, DM alpha (HLA-DMA), were involved in HLA-class I and II clusters, respectively. Another four novel genes, MOG, and those encoding coiled-coil alpha-helical rod protein 1 (CCHCR1), bromodomain-containing protein 2 (BRD2), and chromosome 6 open reading frame 15 (C6orf15), were directly connected with the HLA clusters (Fig. 3).


Susceptibility Genes for Multiple Sclerosis Identified in a Gene-Based Genome-Wide Association Study.

Lin X, Deng FY, Lu X, Lei SF - J Clin Neurol (2015)

Protein-protein interactions between MS-associated genes. Only the connected genes are shown. The novel genes are labeled in red. Different line colors represent the types of evidence for the association. HLA class I cluster: major histocompatibility complex, class I, A (HLA-A), Major histocompatibility complex, class I, C (HLA-C), and major histocompatibility complex, class I, F (HLA-F); HLA class II cluster: major histocompatibility complex, class II, DQ alpha 1 (HLA-DQA1), major histocompatibility complex, class II, DQ alpha 2 (HLA-DQA2), major histocompatibility complex, class II, DQ beta 2 (HLA-DQB2), major histocompatibility complex, class II, DR alha (HLA-DRA), major histocompatibility complex, class II, DO beta (HLA-DOB), major histocompatibility complex, class II, DM alpha (HLA-DMA), and major histocompatibility complex, class II, DM beta (HLA-DMB). HLA: human leukocyte antigen, MS: Multiple sclerosis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4596110&req=5

Figure 3: Protein-protein interactions between MS-associated genes. Only the connected genes are shown. The novel genes are labeled in red. Different line colors represent the types of evidence for the association. HLA class I cluster: major histocompatibility complex, class I, A (HLA-A), Major histocompatibility complex, class I, C (HLA-C), and major histocompatibility complex, class I, F (HLA-F); HLA class II cluster: major histocompatibility complex, class II, DQ alpha 1 (HLA-DQA1), major histocompatibility complex, class II, DQ alpha 2 (HLA-DQA2), major histocompatibility complex, class II, DQ beta 2 (HLA-DQB2), major histocompatibility complex, class II, DR alha (HLA-DRA), major histocompatibility complex, class II, DO beta (HLA-DOB), major histocompatibility complex, class II, DM alpha (HLA-DMA), and major histocompatibility complex, class II, DM beta (HLA-DMB). HLA: human leukocyte antigen, MS: Multiple sclerosis.
Mentions: The 58 identified MS-associated genes were retrieved from the STRING database. Only 36 genes, including 10 novel genes, were annotated in this database. The genes at the HLA regions were clearly enriched into two clusters: HLA class I and II clusters (Fig. 3). Two novel genes, those encoding major histocompatibility complex, class, I, A (HLA-A) and major histocompatibility complex, class II, DM alpha (HLA-DMA), were involved in HLA-class I and II clusters, respectively. Another four novel genes, MOG, and those encoding coiled-coil alpha-helical rod protein 1 (CCHCR1), bromodomain-containing protein 2 (BRD2), and chromosome 6 open reading frame 15 (C6orf15), were directly connected with the HLA clusters (Fig. 3).

Bottom Line: The aim of this study was to identify more genes associated with MS.A total of 58 genes was identified, including 20 "novel" genes significantly associated with MS (p<1.40×10⁻⁴).The results of this study emphasize the high power of gene-based GWAS in detecting the susceptibility genes of MS.

View Article: PubMed Central - PubMed

Affiliation: Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu, People's Republic of China.

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<1.40×10⁻⁴). 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.

No MeSH data available.


Related in: MedlinePlus