Validation of tag SNPs for multiple sclerosis HLA risk alleles across the 1000 genomes panel.

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  • Additional Information
    • Source:
      Publisher: Elsevier/North-Holland Country of Publication: United States NLM ID: 8010936 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-1166 (Electronic) Linking ISSN: 01988859 NLM ISO Abbreviation: Hum Immunol Subsets: MEDLINE
    • Publication Information:
      Original Publication: [New York] Elsevier/North-Holland.
    • Subject Terms:
      Multiple Sclerosis*/genetics ; Polymorphism, Single Nucleotide* ; Genetic Predisposition to Disease* ; Alleles* ; Linkage Disequilibrium* ; Gene Frequency*; Humans ; HLA-DQ beta-Chains/genetics ; HLA-DRB1 Chains/genetics ; Genome, Human ; Risk
    • Abstract:
      Currently, the genetic variants strongly associated with risk for Multiple Sclerosis (MS) are located in the Major Histocompatibility Complex. This includes DRB1*15:01 and DRB1*15:03 alleles at the HLA-DRB1 locus, the latter restricted to African populations; the DQB1*06:02 allele at the HLA-DQB1 locus which is in high linkage disequilibrium (LD) with DRB1*15:01; and protective allele A*02:01 at the HLA-A locus. HLA allele identification is facilitated by co-inherited ('tag') single nucleotide polymorphisms (SNPs); however, SNP validation is not typically done outside of the discovery population. We examined 19 SNPs reported to be in high LD with these alleles in 2,502 healthy subjects included in the 1000 Genomes panel having typed HLA data. Examination of 3 indices (LD R 2 values, sensitivity and specificity, minor allele frequency) revealed few SNPs with high tagging performance. All SNPs examined that tag DRB1*15:01 were in perfect LD in the British population; three showed high tagging performance in 4 of the 5 European, and 2 of the 4 American populations. For DQB1*06:02, with no previously validated tag SNPs, we show that rs3135388 has high tagging performance in one South Asian, one American, and one European population. We identify for the first time that rs2844821 has high tagging performance for A*02:01 in 5 of 7 African populations including African Americans, and 4 of the 5 European populations. These results provide a basis for selecting SNPs with high tagging performance to assess HLA alleles across diverse populations, for MS risk as well as for other diseases and conditions.
      Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Published by Elsevier Inc.)
    • Grant Information:
      I01 BX002625 United States BX BLRD VA; IK6 BX004852 United States BX BLRD VA
    • Contributed Indexing:
      Keywords: 1000 genomes; HLA; MHC; Multiple sclerosis; Single nucleotide polymorphism
    • Accession Number:
      0 (HLA-DQ beta-Chains)
      0 (HLA-DRB1 Chains)
      0 (HLA-DQB1 antigen)
    • Publication Date:
      Date Created: 20240404 Date Completed: 20240602 Latest Revision: 20240602
    • Publication Date:
      20240603
    • Accession Number:
      10.1016/j.humimm.2024.110790
    • Accession Number:
      38575482