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HLA Class I and Genetic Susceptibility to Type 1 Diabetes Results From the Type 1 Diabetes Genetics Consortium

Noble, Janelle A.; Valdes, Ana Maria; Varney, Michael D.; Carlson, Joyce LU ; Moonsamy, Priscilla; Fear, Anna Lisa; Lane, Julie A.; Lavant, Eva; Rappner, Rebecca and Louey, Anthony, et al. (2010) In Diabetes 59(11). p.2972-2979
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. RESEARCH DESIGN AND 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... (More)
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. RESEARCH DESIGN AND 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 x 10(-11)) and B*3906 (10.31; P = 4 X 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 H. Other class I type 1 diabetes associations appear to be specific to individual class H 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 H alleles, are associated with type 1 diabetes. Diabetes 59:2972-2979, 2010 (Less)
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Contribution to journal
publication status
published
subject
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Diabetes
volume
59
issue
11
pages
2972 - 2979
publisher
American Diabetes Association Inc.
external identifiers
  • wos:000284133400036
  • scopus:78049246370
ISSN
1939-327X
DOI
10.2337/db10-0699
language
English
LU publication?
yes
id
871050d7-7900-4422-ab89-63924193d955 (old id 1752238)
date added to LUP
2011-01-04 07:42:27
date last changed
2018-07-15 03:56:20
@article{871050d7-7900-4422-ab89-63924193d955,
  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. RESEARCH DESIGN AND 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 x 10(-11)) and B*3906 (10.31; P = 4 X 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 H. Other class I type 1 diabetes associations appear to be specific to individual class H 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 H alleles, are associated with type 1 diabetes. Diabetes 59:2972-2979, 2010},
  author       = {Noble, Janelle A. and Valdes, Ana Maria and Varney, Michael D. and Carlson, Joyce and Moonsamy, Priscilla and Fear, Anna Lisa and Lane, Julie A. and Lavant, Eva and Rappner, Rebecca and Louey, Anthony and Concannon, Patrick and Mychaleckyj, Josyf C. and Erlich, Henry A.},
  issn         = {1939-327X},
  language     = {eng},
  number       = {11},
  pages        = {2972--2979},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {HLA Class I and Genetic Susceptibility to Type 1 Diabetes Results From the Type 1 Diabetes Genetics Consortium},
  url          = {http://dx.doi.org/10.2337/db10-0699},
  volume       = {59},
  year         = {2010},
}