title: Genetic contribution to multiple sclerosis risk among Ashkenazi Jews.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA. Pouya.Khankhanian@ucsf.edu.
authors.forename: Pouya
authors.initials: P
authors.lastname: Khankhanian
authors.affiliation: Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA. matusita@neuro.med.kyushu-u.ac.jp.|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.
authors.forename: Takuya
authors.initials: T
authors.lastname: Matsushita
authors.affiliation: Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA. Lohith.Madireddy@ucsf.edu.
authors.forename: Lohith
authors.initials: L
authors.lastname: Madireddy
authors.affiliation: Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA. Antoine.Lizee@ucsf.edu.
authors.forename: Antoine
authors.initials: A
authors.lastname: Lizée
authors.affiliation: Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA. lennoxd@berkeley.edu.
authors.forename: Lennox
authors.initials: L
authors.lastname: Din
authors.affiliation: Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA. Jayaji.More@ucsf.edu.
authors.forename: Jayaji M
authors.initials: JM
authors.lastname: Moré
authors.affiliation: Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA. pierreantoine.gourraud@ucsf.edu.
authors.forename: Pierre-Antoine
authors.initials: PA
authors.lastname: Gourraud
authors.affiliation: Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA. hausers@neurology.ucsf.edu.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hauser
authors.affiliation: Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA. sebaran@cgl.ucsf.edu.
authors.forename: Sergio E
authors.initials: SE
authors.lastname: Baranzini
authors.affiliation: Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA. Jorge.Oksenberg@ucsf.edu.
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Oksenberg
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D005190:Family; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D055106:Genome-Wide Association Study; D015234:HLA-A Antigens / Q000235:genetics; D059945:HLA-B38 Antigen / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007585:Jews / Q000235:genetics* / Q000706:statistics & numerical data; D008297:Male; D009103:Multiple Sclerosis / Q000208:ethnology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D015234:HLA-A Antigens; C053029:HLA-A*68 antigen; D059945:HLA-B38 Antigen; D015236:HLA-C Antigens; C446263:HLA-C*12:03 antigen