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Use of class I and class II HLA loci for predicting age at onset of type 1 diabetes in multiple populations

Valdes, A. M.; Erlich, H. A.; Carlson, Joyce LU ; Varney, M.; Moonsamy, P. V. and Noble, J. A. (2012) In Diabetologia 55(9). p.2394-2401
Abstract
The study aimed to assess, in multiple populations, the role of HLA alleles on early and late age at onset of type 1 diabetes. Stepwise linear regression models were used to determine which HLA class I and class II risk alleles to include. High-resolution genotyping data for patients from the Type 1 Diabetes Genetics Consortium (T1DGC) collection (n = 2,278) and four independent cohorts from Denmark, Sardinia and the USA (Human Biological Data Interchange [HBDI] and Joslin Diabetes Center) (n = 1,324) (total n = 3,602) were used to assess the role of HLA variation on age of onset and predict early onset (age a parts per thousand currency sign5 years) and late onset (age a parts per thousand yen15 years) of type 1 diabetes. In addition to... (More)
The study aimed to assess, in multiple populations, the role of HLA alleles on early and late age at onset of type 1 diabetes. Stepwise linear regression models were used to determine which HLA class I and class II risk alleles to include. High-resolution genotyping data for patients from the Type 1 Diabetes Genetics Consortium (T1DGC) collection (n = 2,278) and four independent cohorts from Denmark, Sardinia and the USA (Human Biological Data Interchange [HBDI] and Joslin Diabetes Center) (n = 1,324) (total n = 3,602) were used to assess the role of HLA variation on age of onset and predict early onset (age a parts per thousand currency sign5 years) and late onset (age a parts per thousand yen15 years) of type 1 diabetes. In addition to carriage of HLA class I alleles A*24:02, B*39:06, B*44:03 and B*18:01, HLA class II DRB1-DQB1 loci significantly contributed to age at onset, explaining 3.4% of its variance in the combined data. HLA genotypes, together with sex, were able to predict late onset in all cohorts studied, with AUC values ranging from 0.58 to 0.63. Similar AUC values (0.59-0.70) were obtained for early onset for most cohorts, except in the Sardinian study, in which none of the models tested had significant predictive power. HLA associations with age of onset are consistent across most white populations and HLA information can predict some of the risk of early and late onset of type 1 diabetes. Considerable heterogeneity was observed between Sardinian and other populations, particularly with regard to early age of onset. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Age at onset, HLA, Risk prediction, ROC curve, Type 1 diabetes, Type 1, diabetes genetics consortium, T1DGC
in
Diabetologia
volume
55
issue
9
pages
2394 - 2401
publisher
Springer Verlag
external identifiers
  • wos:000307301800015
  • scopus:84866107950
ISSN
1432-0428
DOI
10.1007/s00125-012-2608-z
language
English
LU publication?
yes
id
b61bc763-2a15-4478-8069-261f1d413283 (old id 3055699)
date added to LUP
2012-10-05 07:16:58
date last changed
2017-11-12 03:05:56
@article{b61bc763-2a15-4478-8069-261f1d413283,
  abstract     = {The study aimed to assess, in multiple populations, the role of HLA alleles on early and late age at onset of type 1 diabetes. Stepwise linear regression models were used to determine which HLA class I and class II risk alleles to include. High-resolution genotyping data for patients from the Type 1 Diabetes Genetics Consortium (T1DGC) collection (n = 2,278) and four independent cohorts from Denmark, Sardinia and the USA (Human Biological Data Interchange [HBDI] and Joslin Diabetes Center) (n = 1,324) (total n = 3,602) were used to assess the role of HLA variation on age of onset and predict early onset (age a parts per thousand currency sign5 years) and late onset (age a parts per thousand yen15 years) of type 1 diabetes. In addition to carriage of HLA class I alleles A*24:02, B*39:06, B*44:03 and B*18:01, HLA class II DRB1-DQB1 loci significantly contributed to age at onset, explaining 3.4% of its variance in the combined data. HLA genotypes, together with sex, were able to predict late onset in all cohorts studied, with AUC values ranging from 0.58 to 0.63. Similar AUC values (0.59-0.70) were obtained for early onset for most cohorts, except in the Sardinian study, in which none of the models tested had significant predictive power. HLA associations with age of onset are consistent across most white populations and HLA information can predict some of the risk of early and late onset of type 1 diabetes. Considerable heterogeneity was observed between Sardinian and other populations, particularly with regard to early age of onset.},
  author       = {Valdes, A. M. and Erlich, H. A. and Carlson, Joyce and Varney, M. and Moonsamy, P. V. and Noble, J. A.},
  issn         = {1432-0428},
  keyword      = {Age at onset,HLA,Risk prediction,ROC curve,Type 1 diabetes,Type 1,diabetes genetics consortium,T1DGC},
  language     = {eng},
  number       = {9},
  pages        = {2394--2401},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {Use of class I and class II HLA loci for predicting age at onset of type 1 diabetes in multiple populations},
  url          = {http://dx.doi.org/10.1007/s00125-012-2608-z},
  volume       = {55},
  year         = {2012},
}