Genetic contribution to multiple sclerosis risk among Ashkenazi Jews

Pouya Khankhanian, Takuya Matsushita, Lohith Madireddy, Antoine Lizée, Lennox Din, Jayaji M. Moré, Pierre Antoine Gourraud, Stephen L. Hauser, Sergio E. Baranzini, Jorge R. Oksenberg

    研究成果: ジャーナルへの寄稿記事

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    抄録

    Background: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, with a strong genetic component. Over 100 genetic loci have been implicated in susceptibility to MS in European populations, the most prominent being the 15:01 allele of the HLA-DRB1 gene. The prevalence of MS is high in European populations including those of Ashkenazi origin, and low in African and Asian populations including those of Jewish origin. Methods: Here we identified and extracted a total of 213 Ashkenazi MS cases and 546 ethnically matched healthy control individuals from two previous genome-wide case-control association analyses, and 72 trios (affected proband and two unaffected parents) from a previous genome-wide transmission disequilibrium association study, using genetic data to define Ashkenazi. We compared the pattern of genetic risk between Ashkenazi and non-Ashkenazi Europeans. We also sought to identify novel Ashkenazi-specific risk loci by performing association tests on the subset of Ashkenazi cases, controls, probands, and parents from each study. Results: The HLA-DRB1*15:01 allele and the non-HLA risk alleles were present at relatively low frequencies among Ashkenazi and explained a smaller fraction of the population-level risk when compared to non-Ashkenazi Europeans. Alternative HLA susceptibility alleles were identified in an Ashkenazi-only association study, including HLA-A*68:02 and one or both genes in the HLA-B*38:01-HLA-C*12:03 haplotype. The genome-wide screen in Ashkenazi did not reveal any loci associated with MS risk. Conclusion: These results suggest that genetic susceptibility to MS in Ashkenazi Jews has not been as well established as that of non-Ashkenazi Europeans. This implies value in studying large well-characterized Ashkenazi populations to accelerate gene discovery in complex genetic diseases.

    元の言語英語
    記事番号55
    ジャーナルBMC Medical Genetics
    16
    発行部数1
    DOI
    出版物ステータス出版済み - 7 28 2015

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    Jews
    Multiple Sclerosis
    Alleles
    HLA-DRB1 Chains
    Population
    Genetic Association Studies
    Genome
    Autoimmune Diseases of the Nervous System
    Parents
    HLA-C Antigens
    Inborn Genetic Diseases
    Genetic Loci
    HLA-B Antigens
    Genetic Predisposition to Disease
    Haplotypes
    Genes
    Central Nervous System

    All Science Journal Classification (ASJC) codes

    • Genetics
    • Genetics(clinical)

    これを引用

    Khankhanian, P., Matsushita, T., Madireddy, L., Lizée, A., Din, L., Moré, J. M., ... Oksenberg, J. R. (2015). Genetic contribution to multiple sclerosis risk among Ashkenazi Jews. BMC Medical Genetics, 16(1), [55]. https://doi.org/10.1186/s12881-015-0201-2

    Genetic contribution to multiple sclerosis risk among Ashkenazi Jews. / Khankhanian, Pouya; Matsushita, Takuya; Madireddy, Lohith; Lizée, Antoine; Din, Lennox; Moré, Jayaji M.; Gourraud, Pierre Antoine; Hauser, Stephen L.; Baranzini, Sergio E.; Oksenberg, Jorge R.

    :: BMC Medical Genetics, 巻 16, 番号 1, 55, 28.07.2015.

    研究成果: ジャーナルへの寄稿記事

    Khankhanian, P, Matsushita, T, Madireddy, L, Lizée, A, Din, L, Moré, JM, Gourraud, PA, Hauser, SL, Baranzini, SE & Oksenberg, JR 2015, 'Genetic contribution to multiple sclerosis risk among Ashkenazi Jews', BMC Medical Genetics, 巻. 16, 番号 1, 55. https://doi.org/10.1186/s12881-015-0201-2
    Khankhanian, Pouya ; Matsushita, Takuya ; Madireddy, Lohith ; Lizée, Antoine ; Din, Lennox ; Moré, Jayaji M. ; Gourraud, Pierre Antoine ; Hauser, Stephen L. ; Baranzini, Sergio E. ; Oksenberg, Jorge R. / Genetic contribution to multiple sclerosis risk among Ashkenazi Jews. :: BMC Medical Genetics. 2015 ; 巻 16, 番号 1.
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    abstract = "Background: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, with a strong genetic component. Over 100 genetic loci have been implicated in susceptibility to MS in European populations, the most prominent being the 15:01 allele of the HLA-DRB1 gene. The prevalence of MS is high in European populations including those of Ashkenazi origin, and low in African and Asian populations including those of Jewish origin. Methods: Here we identified and extracted a total of 213 Ashkenazi MS cases and 546 ethnically matched healthy control individuals from two previous genome-wide case-control association analyses, and 72 trios (affected proband and two unaffected parents) from a previous genome-wide transmission disequilibrium association study, using genetic data to define Ashkenazi. We compared the pattern of genetic risk between Ashkenazi and non-Ashkenazi Europeans. We also sought to identify novel Ashkenazi-specific risk loci by performing association tests on the subset of Ashkenazi cases, controls, probands, and parents from each study. Results: The HLA-DRB1*15:01 allele and the non-HLA risk alleles were present at relatively low frequencies among Ashkenazi and explained a smaller fraction of the population-level risk when compared to non-Ashkenazi Europeans. Alternative HLA susceptibility alleles were identified in an Ashkenazi-only association study, including HLA-A*68:02 and one or both genes in the HLA-B*38:01-HLA-C*12:03 haplotype. The genome-wide screen in Ashkenazi did not reveal any loci associated with MS risk. Conclusion: These results suggest that genetic susceptibility to MS in Ashkenazi Jews has not been as well established as that of non-Ashkenazi Europeans. This implies value in studying large well-characterized Ashkenazi populations to accelerate gene discovery in complex genetic diseases.",
    author = "Pouya Khankhanian and Takuya Matsushita and Lohith Madireddy and Antoine Liz{\'e}e and Lennox Din and Mor{\'e}, {Jayaji M.} and Gourraud, {Pierre Antoine} and Hauser, {Stephen L.} and Baranzini, {Sergio E.} and Oksenberg, {Jorge R.}",
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    AU - Khankhanian, Pouya

    AU - Matsushita, Takuya

    AU - Madireddy, Lohith

    AU - Lizée, Antoine

    AU - Din, Lennox

    AU - Moré, Jayaji M.

    AU - Gourraud, Pierre Antoine

    AU - Hauser, Stephen L.

    AU - Baranzini, Sergio E.

    AU - Oksenberg, Jorge R.

    PY - 2015/7/28

    Y1 - 2015/7/28

    N2 - Background: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, with a strong genetic component. Over 100 genetic loci have been implicated in susceptibility to MS in European populations, the most prominent being the 15:01 allele of the HLA-DRB1 gene. The prevalence of MS is high in European populations including those of Ashkenazi origin, and low in African and Asian populations including those of Jewish origin. Methods: Here we identified and extracted a total of 213 Ashkenazi MS cases and 546 ethnically matched healthy control individuals from two previous genome-wide case-control association analyses, and 72 trios (affected proband and two unaffected parents) from a previous genome-wide transmission disequilibrium association study, using genetic data to define Ashkenazi. We compared the pattern of genetic risk between Ashkenazi and non-Ashkenazi Europeans. We also sought to identify novel Ashkenazi-specific risk loci by performing association tests on the subset of Ashkenazi cases, controls, probands, and parents from each study. Results: The HLA-DRB1*15:01 allele and the non-HLA risk alleles were present at relatively low frequencies among Ashkenazi and explained a smaller fraction of the population-level risk when compared to non-Ashkenazi Europeans. Alternative HLA susceptibility alleles were identified in an Ashkenazi-only association study, including HLA-A*68:02 and one or both genes in the HLA-B*38:01-HLA-C*12:03 haplotype. The genome-wide screen in Ashkenazi did not reveal any loci associated with MS risk. Conclusion: These results suggest that genetic susceptibility to MS in Ashkenazi Jews has not been as well established as that of non-Ashkenazi Europeans. This implies value in studying large well-characterized Ashkenazi populations to accelerate gene discovery in complex genetic diseases.

    AB - Background: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, with a strong genetic component. Over 100 genetic loci have been implicated in susceptibility to MS in European populations, the most prominent being the 15:01 allele of the HLA-DRB1 gene. The prevalence of MS is high in European populations including those of Ashkenazi origin, and low in African and Asian populations including those of Jewish origin. Methods: Here we identified and extracted a total of 213 Ashkenazi MS cases and 546 ethnically matched healthy control individuals from two previous genome-wide case-control association analyses, and 72 trios (affected proband and two unaffected parents) from a previous genome-wide transmission disequilibrium association study, using genetic data to define Ashkenazi. We compared the pattern of genetic risk between Ashkenazi and non-Ashkenazi Europeans. We also sought to identify novel Ashkenazi-specific risk loci by performing association tests on the subset of Ashkenazi cases, controls, probands, and parents from each study. Results: The HLA-DRB1*15:01 allele and the non-HLA risk alleles were present at relatively low frequencies among Ashkenazi and explained a smaller fraction of the population-level risk when compared to non-Ashkenazi Europeans. Alternative HLA susceptibility alleles were identified in an Ashkenazi-only association study, including HLA-A*68:02 and one or both genes in the HLA-B*38:01-HLA-C*12:03 haplotype. The genome-wide screen in Ashkenazi did not reveal any loci associated with MS risk. Conclusion: These results suggest that genetic susceptibility to MS in Ashkenazi Jews has not been as well established as that of non-Ashkenazi Europeans. This implies value in studying large well-characterized Ashkenazi populations to accelerate gene discovery in complex genetic diseases.

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