title: HLA class I and genetic susceptibility to type 1 diabetes: results from the Type 1 Diabetes Genetics Consortium.
abstract: OBJECTIVE
  We report here genotyping data and type 1 diabetes association analyses for HLA class I loci (A, B, and C) on 1,753 multiplex pedigrees from the Type 1 Diabetes Genetics Consortium (T1DGC), a large international collaborative study.
  
  
  METHODS
  Complete eight-locus HLA genotyping data were generated. Expected patient class I (HLA-A, -B, and -C) allele frequencies were calculated, based on linkage disequilibrium (LD) patterns with observed HLA class II DRB1-DQA1-DQB1 haplotype frequencies. Expected frequencies were compared to observed allele frequencies in patients.
  
  
  RESULTS
  Significant type 1 diabetes associations were observed at all class I HLA loci. After accounting for LD with HLA class II, the most significantly type 1 diabetes-associated alleles were B*5701 (odds ratio 0.19; P = 4 × 10(-11)) and B*3906 (10.31; P = 4 × 10(-10)). Other significantly type 1 diabetes-associated alleles included A*2402, A*0201, B*1801, and C*0501 (predisposing) and A*1101, A*3201, A*6601, B*0702, B*4403, B*3502, C*1601, and C*0401 (protective). Some alleles, notably B*3906, appear to modulate the risk of all DRB1-DQA1-DQB1 haplotypes on which they reside, suggesting a class I effect that is independent of class II. Other class I type 1 diabetes associations appear to be specific to individual class II haplotypes. Some apparent associations (e.g., C*1601) could be attributed to strong LD to another class I susceptibility locus (B*4403).
  
  
  CONCLUSIONS
  These data indicate that HLA class I alleles, in addition to and independently from HLA class II alleles, are associated with type 1 diabetes.
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, California, USA. jnoble@chori.org
authors.forename: Janelle A
authors.initials: JA
authors.lastname: Noble
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Valdes
authors.forename: Michael D
authors.initials: MD
authors.lastname: Varney
authors.forename: Joyce A
authors.initials: JA
authors.lastname: Carlson
authors.forename: Priscilla
authors.initials: P
authors.lastname: Moonsamy
authors.forename: Anna Lisa
authors.initials: AL
authors.lastname: Fear
authors.forename: Julie A
authors.initials: JA
authors.lastname: Lane
authors.forename: Eva
authors.initials: E
authors.lastname: Lavant
authors.forename: Rebecca
authors.initials: R
authors.lastname: Rappner
authors.forename: Anthony
authors.initials: A
authors.lastname: Louey
authors.forename: Patrick
authors.initials: P
authors.lastname: Concannon
authors.forename: Josyf C
authors.initials: JC
authors.lastname: Mychaleckyj
authors.forename: Henry A
authors.initials: HA
authors.lastname: Erlich
mesh_terms: D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005091:Exons; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000473:pathology; D015810:Linkage Disequilibrium; D008297:Male; D011110:Polymorphism, Genetic; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D015395:Histocompatibility Antigens Class I
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