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BMC Med Genet. 2015 Jul 28;16:55. doi: 10.1186/s12881-015-0201-2.

Genetic contribution to multiple sclerosis risk among Ashkenazi Jews.

Author information

1
Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA. Pouya.Khankhanian@ucsf.edu.
2
Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA. matusita@neuro.med.kyushu-u.ac.jp.
3
Current address: Graduate School of Medical Sciences, Kyushu University School of Medicine, 3-1-1, Maidashi, Higashi-ku, Fukuoka City, 812-8582, Japan. matusita@neuro.med.kyushu-u.ac.jp.
4
Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA. Lohith.Madireddy@ucsf.edu.
5
Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA. Antoine.Lizee@ucsf.edu.
6
Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA. lennoxd@berkeley.edu.
7
Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA. Jayaji.More@ucsf.edu.
8
Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA. pierreantoine.gourraud@ucsf.edu.
9
Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA. hausers@neurology.ucsf.edu.
10
Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA. sebaran@cgl.ucsf.edu.
11
Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA. Jorge.Oksenberg@ucsf.edu.

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.

PMID:
26212423
PMCID:
PMC4557862
DOI:
10.1186/s12881-015-0201-2
[Indexed for MEDLINE]
Free PMC Article

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