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Risk alleles for multiple sclerosis in multiplex families.

Abstract

OBJECTIVE

We assessed the hypotheses that non-major histocompatibility complex multiple sclerosis (MS) susceptibility loci would be common to sporadic cases and multiplex families, that they would have larger effects in multiplex families, and that the aggregation of susceptibility loci contributes to the increased prevalence of MS in such families.

METHODS

A set of 43 multiplex families comprising 732 individuals and 211 affected subjects was genotyped for 13 MS candidate genes identified by genome-wide association. A control data set of 182 healthy individuals was also genotyped to perform a case-control analysis alongside the family-based pedigree disequilibrium association test, although this may have been underpowered.

RESULTS

An effect of the IL2RA and CD58 loci was shown in multiplex families as in sporadic MS. The aggregate of the IL2RA, IL7R, EVI5, KIAA0350, and CD58 risk genotypes in affected individuals from multiplex families was found to be notably different from controls (chi(2) = 112, p = 1 x 10(-22)).

CONCLUSIONS

Although differences between individual families can only be suggested, the aggregate results in multiplex families demonstrate effect sizes that are increased as compared with those reported in previous studies for sporadic cases. In addition, they imply that concentrations of susceptibility alleles at IL2RA, IL7R, EVI5, KIAA0350, and CD58 are partly responsible for the heightened prevalence of multiple sclerosis within multiplex families.

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  • Authors+Show Affiliations

    ,

    Wellcome Trust Centre for Human Genetics, Department of Clinical Neurology, University of Oxford, UK.

    , , , , , , ,

    Source

    Neurology 72:23 2009 Jun 09 pg 1984-8

    MeSH

    Alleles
    CD58 Antigens
    Case-Control Studies
    Chromosome Mapping
    DNA Mutational Analysis
    Family
    Female
    Gene Frequency
    Genetic Predisposition to Disease
    Genetic Testing
    Genetic Variation
    Genome-Wide Association Study
    Genotype
    Histocompatibility Antigens
    Humans
    Interleukin-2 Receptor alpha Subunit
    Lectins, C-Type
    Linkage Disequilibrium
    Male
    Molecular Epidemiology
    Monosaccharide Transport Proteins
    Multiple Sclerosis
    Nuclear Proteins
    Pedigree
    Polymorphism, Single Nucleotide
    Prevalence
    Receptors, Interleukin-7
    Risk Factors

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    19506219

    Citation

    D'Netto, M J., et al. "Risk Alleles for Multiple Sclerosis in Multiplex Families." Neurology, vol. 72, no. 23, 2009, pp. 1984-8.
    D'Netto MJ, Ward H, Morrison KM, et al. Risk alleles for multiple sclerosis in multiplex families. Neurology. 2009;72(23):1984-8.
    D'Netto, M. J., Ward, H., Morrison, K. M., Ramagopalan, S. V., Dyment, D. A., DeLuca, G. C., ... Ebers, G. C. (2009). Risk alleles for multiple sclerosis in multiplex families. Neurology, 72(23), pp. 1984-8. doi:10.1212/WNL.0b013e3181a92c25.
    D'Netto MJ, et al. Risk Alleles for Multiple Sclerosis in Multiplex Families. Neurology. 2009 Jun 9;72(23):1984-8. PubMed PMID: 19506219.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Risk alleles for multiple sclerosis in multiplex families. AU - D'Netto,M J, AU - Ward,H, AU - Morrison,K M, AU - Ramagopalan,S V, AU - Dyment,D A, AU - DeLuca,G C, AU - Handunnetthi,L, AU - Sadovnick,A D, AU - Ebers,G C, PY - 2009/6/10/entrez PY - 2009/6/10/pubmed PY - 2009/8/4/medline SP - 1984 EP - 8 JF - Neurology JO - Neurology VL - 72 IS - 23 N2 - OBJECTIVE: We assessed the hypotheses that non-major histocompatibility complex multiple sclerosis (MS) susceptibility loci would be common to sporadic cases and multiplex families, that they would have larger effects in multiplex families, and that the aggregation of susceptibility loci contributes to the increased prevalence of MS in such families. METHODS: A set of 43 multiplex families comprising 732 individuals and 211 affected subjects was genotyped for 13 MS candidate genes identified by genome-wide association. A control data set of 182 healthy individuals was also genotyped to perform a case-control analysis alongside the family-based pedigree disequilibrium association test, although this may have been underpowered. RESULTS: An effect of the IL2RA and CD58 loci was shown in multiplex families as in sporadic MS. The aggregate of the IL2RA, IL7R, EVI5, KIAA0350, and CD58 risk genotypes in affected individuals from multiplex families was found to be notably different from controls (chi(2) = 112, p = 1 x 10(-22)). CONCLUSIONS: Although differences between individual families can only be suggested, the aggregate results in multiplex families demonstrate effect sizes that are increased as compared with those reported in previous studies for sporadic cases. In addition, they imply that concentrations of susceptibility alleles at IL2RA, IL7R, EVI5, KIAA0350, and CD58 are partly responsible for the heightened prevalence of multiple sclerosis within multiplex families. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/19506219/Risk_alleles_for_multiple_sclerosis_in_multiplex_families_ L2 - http://www.neurology.org/cgi/pmidlookup?view=long&pmid=19506219 DB - PRIME DP - Unbound Medicine ER -