TY - JOUR
T1 - Genetic contribution to multiple sclerosis risk among Ashkenazi Jews
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.
N1 - Funding Information:
Genetic data were provided by the International Multiple Sclerosis Genetics Consortium, the GeneMSA Consortium, and the Wellcome Trust Case–control Consortium. This study was supported by the National Institutes of Health (RO1NS26799 and R01NS49477). The funding body did not participate in collection, analysis, and interpretation of data, in the writing of the manuscript, or in the decision to submit the manuscript for publication.
Publisher Copyright:
© 2015 Khankhanian et al.
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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U2 - 10.1186/s12881-015-0201-2
DO - 10.1186/s12881-015-0201-2
M3 - Article
C2 - 26212423
AN - SCOPUS:84937809955
VL - 16
JO - BMC Medical Genetics
JF - BMC Medical Genetics
SN - 1471-2350
IS - 1
M1 - 55
ER -