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Identification of a novel risk locus for multiple sclerosis at 13q31.3 by a pooled genome-wide scan of 500,000 single nucleotide polymorphisms.

Abstract

Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system with an important genetic component and strongest association driven by the HLA genes. We performed a pooling-based genome-wide association study of 500,000 SNPs in order to find new loci associated with the disease. After applying several criteria, 320 SNPs were selected from the microarrays and individually genotyped in a first and independent Spanish Caucasian replication cohort. The 8 most significant SNPs validated in this cohort were also genotyped in a second US Caucasian replication cohort for confirmation. The most significant association was obtained for SNP rs3129934, which neighbors the HLA-DRB/DQA loci and validates our pooling-based strategy. The second strongest association signal was found for SNP rs1327328, which resides in an unannotated region of chromosome 13 but is in linkage disequilibrium with nearby functional elements that may play important roles in disease susceptibility. This region of chromosome 13 has not been previously identified in MS linkage genome screens and represents a novel risk locus for the disease.

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  • Authors+Show Affiliations

    ,

    Unitat de Neuroimmunologia Clínica, CEM-Cat, Hospital Universitari Vall d'Hebron, Barcelona, Spain. mcomabel@ir.vhebron.net

    , , , , , , , ,

    Source

    PloS one 3:10 2008 pg e3490

    MeSH

    Chromosomes, Human, Pair 13
    Cohort Studies
    European Continental Ancestry Group
    Genetic Predisposition to Disease
    Genome, Human
    Genome-Wide Association Study
    Genotype
    HLA-DQ Antigens
    HLA-DR Antigens
    Humans
    Linkage Disequilibrium
    Multiple Sclerosis
    Oligonucleotide Array Sequence Analysis
    Polymorphism, Single Nucleotide

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    18941528

    Citation

    Comabella, Manuel, et al. "Identification of a Novel Risk Locus for Multiple Sclerosis at 13q31.3 By a Pooled Genome-wide Scan of 500,000 Single Nucleotide Polymorphisms." PloS One, vol. 3, no. 10, 2008, pp. e3490.
    Comabella M, Craig DW, Camiña-Tato M, et al. Identification of a novel risk locus for multiple sclerosis at 13q31.3 by a pooled genome-wide scan of 500,000 single nucleotide polymorphisms. PLoS ONE. 2008;3(10):e3490.
    Comabella, M., Craig, D. W., Camiña-Tato, M., Morcillo, C., Lopez, C., Navarro, A., ... Martin, R. (2008). Identification of a novel risk locus for multiple sclerosis at 13q31.3 by a pooled genome-wide scan of 500,000 single nucleotide polymorphisms. PloS One, 3(10), pp. e3490. doi:10.1371/journal.pone.0003490.
    Comabella M, et al. Identification of a Novel Risk Locus for Multiple Sclerosis at 13q31.3 By a Pooled Genome-wide Scan of 500,000 Single Nucleotide Polymorphisms. PLoS ONE. 2008;3(10):e3490. PubMed PMID: 18941528.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Identification of a novel risk locus for multiple sclerosis at 13q31.3 by a pooled genome-wide scan of 500,000 single nucleotide polymorphisms. AU - Comabella,Manuel, AU - Craig,David W, AU - Camiña-Tato,Montse, AU - Morcillo,Carlos, AU - Lopez,Cristina, AU - Navarro,Arcadi, AU - Rio,Jordi, AU - ,, AU - Montalban,Xavier, AU - Martin,Roland, Y1 - 2008/10/22/ PY - 2008/03/21/received PY - 2008/09/04/accepted PY - 2008/10/23/pubmed PY - 2009/1/14/medline PY - 2008/10/23/entrez SP - e3490 EP - e3490 JF - PloS one JO - PLoS ONE VL - 3 IS - 10 N2 - Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system with an important genetic component and strongest association driven by the HLA genes. We performed a pooling-based genome-wide association study of 500,000 SNPs in order to find new loci associated with the disease. After applying several criteria, 320 SNPs were selected from the microarrays and individually genotyped in a first and independent Spanish Caucasian replication cohort. The 8 most significant SNPs validated in this cohort were also genotyped in a second US Caucasian replication cohort for confirmation. The most significant association was obtained for SNP rs3129934, which neighbors the HLA-DRB/DQA loci and validates our pooling-based strategy. The second strongest association signal was found for SNP rs1327328, which resides in an unannotated region of chromosome 13 but is in linkage disequilibrium with nearby functional elements that may play important roles in disease susceptibility. This region of chromosome 13 has not been previously identified in MS linkage genome screens and represents a novel risk locus for the disease. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/18941528/Identification_of_a_novel_risk_locus_for_multiple_sclerosis_at_13q31_3_by_a_pooled_genome_wide_scan_of_500000_single_nucleotide_polymorphisms_ L2 - http://dx.plos.org/10.1371/journal.pone.0003490 DB - PRIME DP - Unbound Medicine ER -